R33711, a new drug with presumed potent calcium-antagonistic property, was found to suppress the insulinotropic action of glucose and gliclazide but not that of theophylline. A 0.2 µM concentration of R33711 was sufficient to abolish glucose-induced insulin release. At this concentration, R33711 inhibited the net uptake of 45Ca2+ by isolated islets, whether in the absence or presence of either glucose or sulfonylurea. In the isolated islets, R33711 failed to affect the glucose-stimulated production of lactate, the rate of 45Ca2+ efflux, the inhibitory action of glucose upon such an efflux and its increase in response to theophylline. These data are compatible with the view that R33711 inhibits entry of Ca2+ into the B-cell and that integrity of such an inward cationic movement usually plays a permissive role in the maintenance of the Ca2+-dependent insulin secretory process.