Pharmacodynamic studies were performed using tolbutamide, glibenclamide, glibornuride (Ro 6-4563) and glisoxepide (BS 4231). The four compounds were administered intravenously, and exact dose-response relations were established, calculating the ED 30 of the decrease in blood glucose in healthy volunteers. Accordingly, the dose corresponding to the ED 30 was given twice with a three hour interval to maturity-onset diabetics. Different dynamics of insulin response were observed after tolbutamide, glibornuride and glisoxepide on the one hand, and glibenclamide on the other. In contrast to other reports in the literature, an obvious uniformly weaker degree of insulin secretion was seen after each of the different sulphonylurea compounds when given repeatedly.