Diazoxide 5 mg/kg/day was administered to four normal subjects for five days and, together with insulin, to ten diabetic subjects for seven days. In every case there was a substantial increase in the insulin response to combined stimulation of the pancreatic beta cells with 1 mg of glucagon and 2 g of tolbutamide given intravenously. Similar increases were not seen in four diabetics who received placebo with insulin. It is likely that the observed improvements reflected increased insulin stores which resulted from diazoxide inhibition of insulin release. These findings suggest that poor insulin responses in diabetics may be due, at least in part, to chronic overstimulation of the beta cells. Pharmacological agents such as diazoxide, which inhibit glucose-induced insulin release, may have a place in preserving and restoring insulin secretion in diabetes.