David Silverman describes the episode as "one of my very favorite episodes that I had the pleasure to direct". He notes that several "standard Homerisms" appear for the first time in the episode, such as Homer's conversations with his brain and his high-pitched "fairy voice".
The episode includes a first act that is much longer than a normal episode of the show. The producers were going to end the act with Mr. Burns feeling better, but decided to extend it to show how the Simpson family was affected.
Sam Simon, Al Jean and Mike Reiss came up with the idea for the episode while they were trying to fill up the rest of the production run. A co-worker had recently needed a blood transfusion, and the writers thought it would be funny if Mr. Burns had one.
Burns's line about getting "A frabulous, grabulous, zip-zoop-zabulous present" is similar to lines used in Dr. Seuss books.