Inhibition of acid secretion with high doses of antisecretagogues, such as omeprazole, is known to raise the plasma gastrin levels. In the present study, we examined the effect of long-term (1-year) treatment of female rats with high doses of omeprazole on the density of antral gastrin and somatostatin cells. A possible effect on the endocrine cell density (chromogranin A as marker) and mucosal thickness of the colon was also examined. The plasma gastrin level in the omeprazole-treated rats was increased 15-fold compared with the level in the controls. The gastrin cell density, on the other hand, showed only a 2-fold increase. The somatostatin cell density in the omeprazole-treated rats was half that in the controls, indicating an inverse relationship between antral gastrin and somatostatin. In the colonic mucosa, neither the mucosal thickness nor the number of chromogranin-A-containing endocrine cells were affected by the omeprazole-induced hypergastrinemia. The results indicate that long-term acid inhibition results in a sustained hypergastrinemia, a modest and stable antral gastrin cell hyperplasia, antral somatostatin cell hypoplasia and lack of trophic effects in the colon.