In normal siblings of piebald mice, artificial fecal pellets were propelled by peristaltic activity through the large intestine in vitro and were expelled at the anal end. Peristalsis was blocked by lidocaine. Artificial fecal pellets were propelled in the dilated region of the megacolon, but were not propelled in the terminal hypoganglionic segment of the intestine of piebald mice. Retropulsion of artificial fecal pellets occurred in vitro in normal bowel obstructed by a ligature, in the bowel of piebald mice with a narrowed terminal segment, and in the intestine of mice with imperforate anus. The results indicate that the distended portion of the colon of piebald mice is capable of coordinated peristalsis and that accumulation of feces and megacolon are secondary to the terminal obstruction that results from absence of coordinated propulsive activity in the hypoganglionic terminal segment. Reverse peristalsis may be a general response to a distal obstruction.