Homer decides to take Marge and the kids down to Bloodbath Gulch, a ghost town turned tourist destination. On their way there, Homer's car breaks down, right in front of the Springfield Retirement Castle, leaving Grampa to assume that they have come to visit him on his birthday. Homer tries his hardest to start the car up again, but is eventually forced to take Grampa with them after he is able to reach them. While in the town bar, Grampa drinks too much sarsaparilla and just as the family is leaving, says he needs to go to the bathroom. Homer refuses to stop, saying that he needs to get home in time to watch an episode of Inside the Actors Studio featuring F. Murray Abraham. Grampa is forced to hold it in for hours and as a result, his kidneys explode. Homer ignored this at first, thinking he needed a new muffler for the car. Dr. Hibbert informs the family that Grampa does not have much time to live, and that the only way he can be saved is if Homer donates one of his kidneys. Homer happily agrees, and is admired and pampered for it by his wife and kids. However, he becomes frightened after finding out about the risks involved in the operation and, while he makes it to the hospital, jumps out a window at the last minute.
Guilt-ridden and ashamed, Homer deems himself unworthy of living amongst civilized people and decides to start a new life at sea, climbing aboard Captain McAllister's ship, described as "the ship of lost souls" (though the back of the ship reads, "Honeybunch", because McAllister never painted over the name). While there, he meets several strange people including a man who looks and sounds like Peter Lorre, who have their own tales of misery. Homer tells them his story but is kicked off of the ship when he mentions that he ran away and left his father to die. Homer eventually drifts back to shore, where he witnesses a father and son build a sand castle and laments how he never had such a relationship with his own father or his kids. Homer decides determinedly to rectify his mistake and takes off for the hospital, trampling the sand castle in the process.
Homer arrives in time, reconciling with Grampa and apologizing for his behavior, but ultimately panics and flees again when Dr. Hibbert says "...this may sting a little". Homer's mad dash from the hospital is stopped by an oncoming truck. While the driver (Hans Moleman) manages to hit the brakes just in time, one of the cars it was carrying slides off and lands on Homer. Homer later wakes up in traction in a hospital bed, and is greeted by Dr. Hibbert, Marge and the kids. Believing Grampa is dead, Homer sadly vows to visit his grave after he gets better. However Grampa, who is alive and well, appears in the doorway and declares that he's never felt better. From the sheepish look of the others in the room, Homer looks down and discovers that, while he was unconscious, they took out one of his kidneys. Angry at first, Homer vows to get it back, but settles down after his family tells him that he did the right thing for Grampa. They engage in a group hug, and Homer proceeds to consider Bart as a potential donor for himself.