- A pyromaniac, ex-employee of a city oil refinery creates an explosion at the facility which starts a chain-reaction of fires that engulf the entire city.
- William Dudley is a corrupt mayor of a nameless Midwestern U.S. city who has allowed a chemical refinery to be built right in the center of town, far from any river, lake or reservoir. On one typical hot summer day, Herman Stover, a dangerously disturbed employee at the works has been denied an expected promotion and in addition, finds himself fired. He then decides to take his revenge against the works by opening the valves to the storage vats and their interconnecting pipes, flooding the area and sewers with gasoline and chemicals. It doesn't take long for this act of petty vandalism to start a fire, which starts a chain reaction that causes massive explosions at the refinery, destroying it and spreading a mushroom-cloud of flame that soon engulfs the entire metropolis! The drama focuses on a newly built hospital which, like the refinery and all civic buildings that went up during the mayor's crooked administration, is shoddily built and poorly equipped where the head doctor, Frank Whitman, and his staff treat thousands of casualties from the city-fire while the city fire chief Risley keeps in constant contact with the fire companies fighting a losing battle against the fires, and Maggie Grayson, an alcoholic reporter/newscaster, sees it as her chance to make it nationwide with her coverage of the story of the 'city on fire.'—Alfred Jingle
- In a present-day nameless American city, Dr. Frank Whitman (Barry Newman) arrives for work as chief surgeon at Brockhurst Hospital, a newly constructed facility downtown. Although the hospital is open for business, head nurse Andrea Harper (Shelley Winters) complains about a generator that is not fully operational.
Meanwhile, a twice-widowed and wealthy heiress named Diana Brockhurst-Lautrec (Susan Clark), whose $3 million dollar endowment made the hospital possible, arrives in town for the dedication ceremony. In her hotel suite, Diana greets Mayor William Dudley (Leslie Nielsen), who is eager to resume his extramarital affair with her, while she appears ambivalent. From a rooftop across the street, freelance celebrity photographer Terry James (Terry Haig) takes a snapshot of the mayor kissing Diana.
At the studios of CFTM-Channel 10 television, alcoholic host Maggie Grayson (Ava Gardner) reports on the top news stories, including coverage of the hospital dedication.
Elsewhere in the city, Herman Stover (Jonathan Welsh) arrives for work at the Manson Refinery, the ninth largest oil refinery in the world, where he has worked for the last 12 years since it's opening. That morning, he hopes for promotion to foreman, but instead the supervisor Mr. Clark (Earl Pennington) offers him a position in Research and Development. Upset, Stover angrily declines the transfer and Mr. Clark rudely lays Stover off.
While cleaning out his locker, Stover admires an old newspaper clipping he saved about Diana Brockhurst-Lautrec, who has become an obsession for him. Although he does not know Diana, Stover brags to an uninterested co-worker that he and Diana grew up in the same poor neighborhood and attended Sycamore High, before she married a wealthy, older man. Tired of being ignored, Stover decides to get the attention of Diana and everyone else by sabotaging the refinery. He quickly runs through the plant, adjusting dials and levers. Soon, the operators in the control room notice unusual smoke patterns from the stacks and an increase in the pressure gauges. As alarms sound, Stover continues to inflict damage by opening fuel pipes.
Before the dedication ceremony, Dr. Whitman takes a moment to reunite with Diana, a former lover with whom he still has a rapport, and then complains to Mayor Dudley, blaming city politics for the unfinished hospital construction.
Leaving the refinery, Herman Stover changes into a new suit and appears at the outdoor dedication in time for Diana's speech. Meanwhile, engineers stabilize the refinery, but the fuel leakage remains undetected and pours into the city's sewer system. When two welders begin work inside a disposal area, their torches ignite a fire, engulfing them in flames. The blaze quickly spreads through the sewer and causes a chain of explosions that completely destroy the refinery and all the workers in it. The massive blasts are felt as violent tremors throughout the city, collapsing buildings and triggering additional fires.
Taking charge, Dr. Whitman instructs the crowd at the ceremony to help move the injured into the hospital and implements an emergency plan for the facility. Unable to reach the mayor, Fire Chief Risley (Henry Fonda) assumes command and issues orders to mobilize the National Guard and tanker planes.
Trapped at the hospital with no working telephone and an ailing colleague, Mayor Dudley, who has ambitions to be governor, worries about the political fallout from the crisis since he supported the refinery despite public protests about its dangerous proximity to the city.
As burn victims crowd the corridors, Dr. Whitman instructs Nurse Harper to clear out non-essential personnel to make room for incoming wounded. Meanwhile, Diana does her best to assist the medical staff, while Stover remains near and also volunteers, hoping that Diana will notice him.
From the television studio, Maggie reports that the casualties number over 3,000, water pressure is falling due to the lingering summer-long drought and looting has begun. The photographer, Terry James, is badly injured after retrieving the pictures of Diana and the mayor from his burning darkroom. As Terry is loaded into an ambulance, the envelope of photos remains tucked underneath his shirt and later falls into Stover's hands after Terry dies at Brockhurst Hospital.
At Fire Headquarters, while updating a councilman (Cec Linder) about the nearly 200 fires burning across the city, Risley emphasizes that the people at Brockhurst are at risk of suffocating from the firestorm, which will siphon oxygen from the air. Risley's office contacts the television news crew on the roof to set up a broadcast signal with the mayor, who confirms that breathing is becoming more difficult. Then, a series of explosions occur, destroying a supply truck and making the street leading to the hospital impassable for rescue vehicles.
Since the fast and changing winds prevent the use of helicopters, Risley devises a plan for firefighters to create a "water tunnel" outside the facility. However, the hospital's fire hoses must cover the first 100 yards from the doors. As people leave the hospital, the mayor soaks everyone with water, including those on stretchers, so that they will have some protection from the uncontrollable flames in the streets until they reach the firemen's tunnel. Tirelessly, Dr. Whitman directs the medical staff and patients towards the exit while continuing to treat the injured.
In another area of the hospital, Diana assists Mrs. Adams, who is about to give birth. During the delivery, Stover approaches Diana to discuss the incriminating photographs, and she promptly dismisses him. As the final group of evacuees gather at the door, Dr. Whitman finds Diana with Mrs. Adams and her newborn baby and prepares them for evacuation. Feeling rejected amid all his efforts, Stover walks out in a daze and is killed when a scaffolding collapses. Nurse Harper tries to save him, but is also struck down and killed by burning debris. As the last person to leave the hospital, Dr. Whitman must roll in puddles to keep his clothing wet when the water from the hose runs out, and he is nearly trapped by flames on the street, but Mayor Dudley guides him toward an opening before the hospital explodes.
Later a day or so later, at the rescue camp in a quarry outside the destroyed city, Mayor Dudley's reputation is restored when Maggie calls him a "hero" on television, though the Mayor insists that the townspeople themselves are the real heroes. Nearby, Diana and Dr. Whitman kiss and renew their relationship.
In the final scene, Chief Risley, as he leaves headquarters, declares to the staff that it takes one person to set fire and destroy an entire city.
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