Female rats were subjected to various treatments for 10 weeks to study effects on plasma gastrin levels. Intact rats were treated orally with omeprazole, 10 or 400 mumol/kg, ranitidine, 175 + 175 + 350 mumol/kg, or vehicle; antrectomized rats were treated with omeprazole, 400 mumol/kg, or vehicle. In addition to plasma gastrin levels, histidine decarboxylase (HDC) activity, histamine levels and ECL cell density in the oxyntic mucosa were determined. Gastrin levels were increased in unoperated rats treated with the high omeprazole dose and with ranitidine, whereas they were lowered in antrectomized controls. A small increase in plasma gastrin was seen in the low-dose omeprazole group. In antrectomized rats treated with omeprazole, the plasma gastrin level was the same as in intact control rats. The ECL cell density, the activity of HDC and the concentration of histamine in the oxyntic mucosa were found to reflect the plasma gastrin concentration. The results suggest that the changes in ECL cell density are secondary to the changes in plasma gastrin, induced by inhibition of acid secretion or antrectomy. It is concluded that neither omeprazole nor ranitidine per se is likely to induce proliferation of ECL cells.