Quantitative histological and immunocytochemical studies have been carried out on the endocrine cells of the gastrointestinal tract in genetically obese mice and their heterozygous (lean) litter mates. In the ob/ob mice hyperplasia of most of the endocrine (APUD) cells of the gut was found, a condition which can be described as apudosis. Quantitative histology of silver-stained preparations, using a method which demonstrates the majority of endocrine cells, showed a significant degree of hyperplasia in all regions of the gastrointestinal tract, with statistically significant differences in the upper intestine (p = less than 0.001). Quantitative immunocytochemical studies by image analysis showed a difference in both number and hormone content of Gastric Inhibitory Peptide (GIP) (p = less than 0.001) and Enteroglucagon (EG) cells in obese as compared to lean mice. Differences in the case of Secretin (S), Gastrin (G) and Vasoactive Intestinal Peptide (VIP) cells were not great but in the obese mice both S and G cells were present in larger numbers in the lower intestine whereas in the lean, and in normal mice, they are predominant in the upper intestine. Whether these complex gut endocrine changes are primary, or secondary to the metabolic abnormalities seen in the ob/ob mouse, cannot presently be determined.