Long-term toxicological experiments with inhibitors of acid secretion were found to induce hyperplasia and eventually carcinoid tumors of the enterochromaffin-like cells of the oxyntic mucosa. To evaluate the effects of 6 months' treatment with omeprazole in humans, the oxyntic endocrine cells were morphometrically investigated at the ultrastructural level in five patients with active duodenal ulcer. No omeprazole-induced changes were found in the volume density of the total endocrine cell population and specific cell types (including the enterochromaffin-like cell) as well as in the other cytological parameters investigated (number of cell profiles per unit area, mean cross-sectional area of cell profiles, nuclear-cytoplasmic ratio, and density of cytoplasmic secretory granules). Both pretreatment and post-treatment values in our patients with duodenal ulcer significantly differed from those of a previous investigation of healthy volunteers with regard to the volume density of enterochromaffin-like cells and non-granulated cells, which increased, and of D cells, which markedly decreased. The latter result may provide a cellular basis for impairment in the paracrine release of fundic somatostatin in peptic ulcer disease. Finally, morphometric data on endocrine cell volume density provided by electron microscopy were found to correlate with those obtained in the same patients using light microscopy techniques (Grimelius silver impregnation and chromogranin A immunostaining). It is concluded that 6 months' treatment with pharmacological doses of omeprazole is devoid of appreciable trophic effect on endocrine cells of human oxyntic mucosa.