Wildlife photographer Pickett Smith (Sam Elliott) is canoeing alone through a swamp off the coast of Florida, taking pictures of the local flora and fauna. He notices a number of instances of pollution, documenting these as well. Siblings Clint and Karen Crockett (Adam Roarke, Joan Van Ark) are driving in a speedboat nearby. Clint is drunk, and causes a near collision with Pickett's canoe, which overturns. More than a little annoyed, Pickett hurls Clint into the water first chance he gets, much to the amusement of Karen. Together they tow Pickett's canoe back to the island estate owned by Clint and Karen's father, Jason Crockett (Ray Milland). They promise Pickett some dry clothes and offer for him to join their annual family celebration. The celebration is in honor of the 4th of July, as well as several family birthdays, including Jason's.
Jason is an extremely crotchety old man confined to a wheelchair. Due to his immense wealth, the members of his family are used to indulging his every whim, usually at the expense of their own dignity. Jason reluctantly welcomes Pickett, although it becomes clear that they are on opposite ends of the spectrum involving all things pertaining to nature. Pickett has respect for the natural world, while Jason seems furious that he cannot control it. The private island is experiencing an overpopulation of frogs and toads, which Jason is trying to curb by spreading various types of pesticides and poisons. Jason proudly calls himself and his family the "ugly rich", which seem to be true, as the various members of his family seem to be entirely self-absorbed and selfish. The one exception seems to be Karen, who doesn't take everything as seriously as the rest of her family. She and Pickett are attracted to one another.
In private, Jason convinces Pickett to explore the island to examine the way the pesticides have affected the environment. He also asks him to look out for Grover, an employee he sent to the other side of the island to spray more poison and insecticides. While Pickett is hiking, he discovers hordes of dead animals, most of them snakes and frogs. After finding Grover's jeep, he finds Grover himself lying face down in a marsh, his body covered with writhing, poisonous snakes that cling to him possessively. After removing the snakes with a stick, Pickett turns him over to find him dead, his face horribly swollen and disfigured.
After returning to the estate that evening, Pickett doesn't tell anybody about Grover's body until talking to Jason, who thanks him for keeping it quiet. The next morning, as the Crockett family begins to set up for the celebration, other fatalities begin to happen. Michael Crockett (David Gilliam), Jason's younger brother, goes out to check on a downed telephone line and suffers a hideous death. He accidentally shoots himself in the leg, which immobilizes him under a tree with scores of low-hanging moss. To his horror, a horde of tarantulas descend from the tree, biting him all over his body. The moss seems to act on its own as well, binding him tightly. The spider venom begins to paralyze him, and ultimately he is totally cocooned in moss and webs, the tarantulas presumably feeding on his body.
Jason's older sister, Iris (Holly Irving), sends her son Kenneth (Nicholas Cortland) into the greenhouse to gather flowers for a centerpiece. While he is alone in there, scores of lizards enter behind him, swarming over the shelves and knocking over bottles of noxious chemicals until the liquids converge into a toxic cloud of gas, which asphyxiates him.
A little later, Iris herself rushes off into the trees, chasing after a butterfly with a net; she is fond of creating dioramas using real insects and flowers, and she sees a butterfly she is anxious to add to her collection. She is stalked by several snakes, which dangle from from tree branches and approach along the ground. After a group of frogs frighten her off the path into the trees, the snakes attack, and she is confronted by a large rattlesnake. Driven further into the brush, she goes into a panic and stumbles through thick undergrowth, which destroys her hairstyle and clothing. She falls into a dirty ditch filled with leaves and filthy water, emerging covered in leeches. Bloodied from the leeches and disgusted by what has happened to herself, she wanders back to the path and is bitten on the arm by the rattlesnake, resulting in her immediate death.
Nearby is Iris' husband, Stuart (George Skaff), who misses discovering her body by only a few feet. He is cornered by alligators and driven into a shallow marsh, where the gators kill and eat him.
Back at the estate, Kenneth's body is discovered in the greenhouse, much to everybody's horror. His girlfriend, Bella (Judy Pace), is distraught and demands to leave immediately. Jason forbids Kenneth's death to interfere with the plans for the party, resulting in an immediate schism between those who want to leave and those who want to stay in order to placate Jason. Bella leaves with two of the servants, the long-suffering butler Charles (Lance Taylor Sr.) and cook Maybelle (Mae Mercer). Clint agrees to take them across the water in his speedboat to the mainland. Once they reach the other side, the three of them are attacked by seagulls.
After looking around the bait and tackle shop on the pier which is deserted as well as the area, Clint returns to the boat only to see that the line has been tethered and it is drifting to the middle of the lake. Clint swims out to his where he is attacked and bitten to death by various water moccasins. His wife, Jenny (Lynn Borden), witnesses Clint's mishap through a pair of binoculars. Rushing down to the water's edge, she becomes stuck in the mud and is immediately attacked and killed by an alligator snapping turtle.
Pickett and Karen realize there is no choice other than to leave. Jason remains belligerent, determined to continue with the 'celebration', furious that this bizarre course of events has interfered with his plans.
Pickett and Karen head down to the water with Jenny's and Clint's young children, Jay and Tina (Hal Hodges, Dale Willingham). Pickett discovers Jenny's dead body floating in the shallow water, the turtle perched on her submerged head while crabs devour the exposed parts of her body. They shield the children from seeing Jenny's remains and usher them into Pickett's canoe. He paddles them across the water, although their escape is temporarily halted when the canoe becomes stuck on rocks and Pickett is attacked by water moccasins while dislodging it. He escapes unharmed, and they make it to the dock with Pickett fighting off more water moccasins with the paddle and shooting an alligator that attacks.
Just beyond the dock area, the four survivors discover the luggage of Bella, Charles and Maybelle, leaving their ultimate fate undetermined. They reach a nearby road and flag down a passing car, driven by a mother and her young son. The mother offers them a ride to Jefferson City, and she says that the four of them are the only people they've seen for miles... suggesting that maybe the phenomenon is widespread. The boy shows them a large bullfrog that he acquired at summer camp where his mother picked him up...
Back at the estate, Jason is now alone inside the mansion, save for his dog Colonel, surrounded by an increasing army of frogs outside as it begins to get dark. He listens to patriotic music on his Victrola record player, until frogs begin to crash through the glass of the windows. Although he tries to ignore them, the horror of the situation proves too much for him. As the frogs swarm over him, he falls out of his wheelchair and suffers a fatal heart attack on the floor. The frogs have succeeded in destroying their tormentor. In the final shot, all of the lights in the mansion flicker out... implying that nature has won and the rest of humanity is next.