We have studied the role of vitamin D in the regulation of gastrin and gastric somatostatin secretion from the isolated perfused rat stomach. In Ca-deficient vitamin D-deficient rats (Ca(-)D(-) group), the basal and bombesin-stimulated gastrin and gastric somatostatin release (basal IRGa, basal IRS, sigma delta IRGa, and sigma delta IRS) all were significantly lower than in Ca-replete vitamin D-replete rats (Ca(+)D(+) group), and also lower than in Ca-replete vitamin D-deficient rats (Ca(+)D(-) group) except for the basal IRGa. In the Ca(+)D(-) group, the basal IRGa and IRS, and sigma delta IRS were not significantly lower than in the Ca(+)D(+) group. Although there was no significant impairment in basal IRGa, sigma delta IRGa in the Ca(+)D(-) group was significantly lower than in the Ca(+)D(+) control group. Thus, the gastrin and gastric somatostatin secretion from the Ca-deficient vitamin D-deficient rats were impaired. In addition, the impaired gastrin and gastric somatostatin secretions seem to be caused not only by a decrease in serum Ca but also by the reduced effect of the vitamin D on the G and gastric D cells.