Treatment of NMRI mice with cyclosporin A (25 mg/kg body wt) for 11 days caused a marked fall in pancreas insulin content, although plasma glucose and plasma insulin were unchanged. When islets from untreated mice were exposed to cyclosporin A (2 mg/l) in vitro, no effect was seen in the first hour. After 24 h, cyclosporin A had significantly decreased the islet content of insulin. Post-culture microperifusion showed that cyclosporin A for 24 or 72 h inhibited the insulin secretory responsiveness. Verapamil in vivo (0.4 mg/kg body wt per day) or in vitro (37.5 μg/l) did not modify these effects. Verapamil at 25 mg/l suppressed the release of insulin but afforded no obvious protection against cyclosporin A during culture. The beneficial action of verapamil on islets transplanted to the kidney may reflect renal events rather than a primary interaction of drugs in the islets.