We have studied the distribution and abundance of histochemically distinct mast cell subpopulations in the normal small and large intestine of man. One subpopulation has histochemical properties similar to the functionally distinct intestinal mucosal mast cell (MMC) of the rat and the other has properties similar to the widely distributed mast cell found in connective tissues and the peritoneal cavity of many animals. Both subpopulations are present in intestinal epithelium, lamina propria, submucosa and muscularis mucosa, and muscle. However, the subpopulation histochemically similar to the rodent MMC is significantly more abundant than the other in all sites in the large intestine and also in the lamina propria and muscle of the small intestine. It is important to determine whether these histochemically distinct mast cell subpopulations in man differ in their responses to various secretagogues and antiallergic compounds as in the rat.