To elucidate whether sulfonylureas directly influence renin secretion, the effect of tolbutamide, glibenclamide, or chlorpropamide on renin secretion was investigated by using the perfused kidney of the rat. The isolated kidneys of male Wistar rats (200–250 g) were perfused with a medium containing 2 µM tolbutamide, 2 µM glibenclamide, and 2 µM chlorpropamide, respectively. Renin activity significantly increased from a basal value of 11.7 ± 3.6 to a peak value of 20.6 ± 5.5 ng/Ang I/ml/h with tolbutamide, from 14.4 ± 4.6 to 32.7 ± 6.5 ng/Ang I/ml/h with glibenclamide, and from 15.0 ± 4.9 to 30.4 ± 6.1 ng/Ang I/ml/h with chlorpropamide. The cAMP concentration in the effluent was not changed by the addition of the sulfonylureas. In kidneys perfused with a calcium-free medium, glibenclamide produced a significant increase in renin activity from a basal value of 13.4 ± 2.1 to a peak value of 30.6 ± 3.4 ng Ang I/ml/h. These results suggest that sulfonylureas stimulate renin secretion from perfused rat kidneys.