To determine the effect of persistent narrowing of the gastric outlet on peptic ulcer disease, changes in gastric hormones induced by pyloric stenosis were studied in an experimental model in the rat. Pyloric stenosis was created by constricting the pylorus to a 4-mm channel. Changes in serum gastrin and plasma somatostatin concentrations, in the length of the lesser curvature, in the size of the fundic and pyloric regions, and in the G-cell and D-cell counts were determined after 4 and 8 weeks (PS4W and PS8W) and compared with those of control groups. The size of the stomach, the serum gastrin concentration, and the corrected G-cell count (indexed to stomach size) were greater in PS8W than in PS4W rats, and both were greater than in respective controls (p < 0.005). Serum somatostatin concentrations were not different, but the total D-cell count and the corrected D-cell count were higher in PS4W and PS8W rats than in controls. Moreover, the total D-cell count and the corrected D-cell count were greater in PS8W than in PS4W (p < 0.05, p < 0.005).