Present methods of management of juvenile-onset diabetes mellitus do not prevent serious and debilitating complications affecting multiple organ systems. In an effort to reverse advanced forms of these complications, segmental transplantation of the pancreas has been performed on 10 patients, seven of whom simultaneously or subsequently received renal transplants. Long periods of normoglycemia (two to four and one-half years) were achieved in two patients who also maintained transplant kidney function. The course of these two patients is described to illustrate the possible value and limitations of the procedure. These patients had normal blood glucose levels, exhibited repeated normal intravenous glucose tolerance curves, and had repeated normal endogenous insulin levels. Their courses were characterized by (1) absence of problems related to pancreatic exocrine secretions into the bladder; (2) stable eye changes despite some episodes of hemorrhage from preexisting retinopathy; (3) vascular complications, including stroke and gangrene of extremities necessitating amputation despite successful femoropopliteal bypass grafting; (4) peripheral neuropathy; and (5) repeated infections. Both patients succumbed to vascular complications. Thus, pancreatic transplantation can maintain blood glucose and insulin at normal levels for extended periods of time. However, it does not reverse such complications as advanced retinopathy or atherosclerosis. Since the procedure may have value in preventing progression of these complications, it should be evaluated in patients with less advanced complications of diabetes.