SUMMARY: The incidence of megacolon has been studied in an inbred strain of mice (NZY) and in the descendants of NZY mice outcrossed to two other inbred strains (NZC, NZB) and to a fertile pituitary dwarf.The results of this study indicate that megacolon is an inheritable disease associated with “piebald” and that it is transmitted by both males and females.The presenting signs and the appearance of the large intestine in affected animals are described together with the features in the enteric plexus which are characteristic of the disease in mice. Attention is drawn to the presence of aganglionic and hypoganglionic segments of gut and the possibility that the length of the aganglionic segment influences the time of onset of megacolon is discussed.