A program using continuously pumped IVI was devised to restore glycemia of unstable diabetes under ambulatory, fed conditions to that of nondiabetic subjects. Five patients with unstable diabetes were studied. The daily regimen consisted of four meals of equal carbohydrate, fat, and protein content taken at 8 A.M., 2 P.M., 8 P.M., and 2 A.M. and 1 hr of standardized exercise in the second postprandial hour (except after the 2 A.M. meal). Confirmation of physiologic replacement of insulin by the IVI program was possible because four patients had low insulin-binding antibodies and minimal distortion of serum IRI. Best glucose control was achieved by increasing the basal flow rate (mean, 0.15 mU/kg/min) 10-fold from 15 to 60 min after daytime meals and from 15 to 105 min after the 2 A.M. meal and doubling the basal rate overnight. Contrasted to the results with SCI, the IVI program significantly improved the mean blood glucose and mean amplitude of glycemic excursions. The IVI program restored the time to glucose peak and postprandial baseline glucose recovery to normal; the amplitude of glucose increase to peak remained somewhat greater than normal.