We compared the ability of closed-loop intravenous insulin infusion (i.e., an artificial "pancreas"), open-loop continuous subcutaneous insulin infusion, and intensified conventional insulin therapy (preprandial injections of regular insulin, with injection of long-acting zinc-suspension insulin before breakfast) to bring the hyperglycemia of insulin-dependent diabetic subjects to a level comparable to that of normal, nondiabetic subjects. The mean circadian levels of plasma glucose, mean amplitude of glycemic excursions, and M values (defined in Methods) did not significantly differ among the three regimens. Although these levels in the diabetic subjects approximated those in the normal subjects, the levels of plasma insulin, mean amplitude of glycemic excursions, and M values were significantly higher than those in normal subjects (P < 0.01). Therefore, at least on a short-term basis, all three regimens can produce comparable, nearly normal levels of blood sugar in such patients; moreover, closed-loop devices can be used to determine insulin requirements for conventional therapy.