We studied two obese type II diabetic patients before, during, and after 3 yr of continuous iv insulin infusion, delivered by means of totally implanted insulin infusion pumps. Tolerance of the devices was excellent, and no side-effects or episodes of significant hypoglycemia occurred. Glycosuria was eliminated, and mean 24-h plasma glucose and hemoglobin A1c levels decreased in both patients and remained in or near the normal range for 3 yr. Improvements were also noted in serum triglyceride concentrations and vitreous fluorescein concentrations after iv fluorescein injection. Euglycemic insulin clamp studies showed that no significant change in glucose disposal rate occurred after 6 and 12 months of treatment. However, some improvement in insulin secretion during hyperglycemic insulin clamp studies occurred in both patients after 6 months of insulin infusion. Evaluation of the insulin-glycerol mixture used in the pump revealed that moderate degradation of insulin occurred in the pump during the 21-day flow cycle, resulting in 6-12% increases in fasting blood glucose levels; in addition, higher mol wt species of immunoreactive insulin were present in the patients' serum. We conclude that long term continuous iv infusion of insulin using a totally implantable infusion pump is practical in type II diabetic patients, is acceptable to patients, and is capable of providing near-normal glycemic control.