Overnight basal insulin requirements to maintain eugycemia were determined in six insulin-requiring diabetic subjects using a feedback-controlled (closed loop) insulin infusion system. Mean hourly insulin infusion rates, required to maintain plasma glucose concentrations at approximately 100 mg/dl, were remarkably stable from 2400 h to 0600 h; however, a twofold to threefold increase in insulin requirements was observed in each subject between 0600 h and 0900 h. This increase in amount of basal insulin required was not associated with increases in plasma glucagon or growth hormone concentrations, but occurred simultaneously with normal diurnal increases in plasma cortisol. These findings suggest that normal diurnal increases in plasma cortisol, independent of the content of the morning meal, contribute to the increased amount of morning insulin required in diabetic subjects. Programs designed for optimal open loop insulin delivery may benefit from modifications designed to coincide with this increase in amount of basal insulin required in the early morning.