We have evaluated the efficacy of an insulin infusion system in the treatment of juvenile-onset diabetic patients that delivers insulin via the subcutaneous route with a portable pump at constant basal rates with pulse dose increments before meals. Studies in the hospital in 15 diabetic patients for 2–14 days indicated rapid restoration of normal glucose homeostasis. Mean plasma glucose levels on pump therapy averaged 85–90 mg/dl, maximal fluctuations in plasma glucose fell by 50–75%, and glycosuria was eliminated. Minimal plasma glucose values varied between 45 and 67 mg/dl. Cholesterol, triglycerides, and free fatty acids as well as fasting and postprandial branched chain amino acid levels were elevated on conventional treatment but fell to normal after 7 days of pump therapy. Pump treatment also restored to normal increased basal growth hormone levels and excessive exercise-induced rises in growth hormone and catecholamines. Normalization of body fuel metabolism occurred, although the total dose of insulin administered by the pump was no greater than the usual insulin dose given by conventional means. We have treated seven insulin-dependent diabetic patients (aged 13–32 yr) for 3–8 mo outside of the hospital. Patients pursued their usual work or school activities. Mean blood glucose (237 ± 28 mg/dl during conventional therapy) fell to 105 ± 5 mg/dl after 4 wk of pump treatment and was maintained between 80 and 104 mg/dl beyond 8 wk. Total glycosylated hemoglobulin was normalized in all patients within 8 wk, as were cholesterol and triglyceride levels. Symptoms of hypoglycemia and overinsulinization and underinsulinization due to human error was relatively uncommon. No episode of mechanical pump failure occurred in 1110 patient-days of use. We conclude that normalization or near normalization of blood glucose levels and correction of abnormal lipid and amino acid metabolism can be achieved with a portable subcutaneous insulin infusion system when continuously used to treat juvenile-onset diabetic patients. Long-term use of this system may provide a feasible means for determining whether metabolic changes resulting from insulin lack cause the complications of diabetes.