Madman is trying to find Dr. Flem to save a man who was hit by a car. The man gives Madman a list of things to do that set him on an adventure that leads him to fight a criminal organization led by Monstadt. This later leads him to Buzztown.
In Buzztown he discovers a man named Randolph Thompson who murdered his wife, and aims to kill the mayor of Buzztown as well. It is up to Madman to save the Mayor. Luckily, he gets help from an unlikely source.