Twelve female guinea pigs were given estradiol and another 12 testosterone for 18 days. A third group of 15 animals underwent oophorectomy and a group of 8 animals served as controls. Gastric and pancreatic D-cells were quantitated in all four groups. Oophorectomy and androgens significantly increased and estrogens significantly decreased gastric D-cell populations. Additionally, estrogens significantly decreased D-cell population in pancreatic islets. It is concluded that the alterations in gastric and pancreatic D-cell populations, which are induced by sex hormone administration and oophorectomy, possibly reflect a hormonal adaptive attempt to restore gastric secretory functions within the normal range.