The success rate of pancreas transplantation allows us to study in more detail the potential beneficial effects of normoglycemia on secondary complications in diabetes mellitus. We report a prospective follow-up (mean 26 mo) of metabolic control, neuropathy, retinopathy, and peripheral microcirculation in 31 patients with type I (insulin-dependent) diabetes (mean age 33 +/- 1 yr; mean duration of diabetes 21 +/- 1 yr) after combined kidney and segmental pancreas grafting. All patients had normal HbA1 levels. Glucose tolerance (GT), insulin, C-peptide, and glucagon were normal in 22 patients, and impaired oral GT with reduced insulin secretory capacity was seen in 9 patients. During follow-up, there was no deterioration of GT and insulin release. Vascular risk factors, e.g., hypertension, cholesterol, and triglycerides, decreased after grafting. Autonomic neuropathy improved clinically, and R-R variation increased significantly in 3 of 18 patients. Peripheral neuropathy improved clinically in 46% of patients and did not deteriorate in the others. Motor nerve conduction velocity increased greater than 20% in 8, less than 20% in 12, and was unchanged in 8 of 28 recipients. Most of the patients (n = 30) had pretransplant laser treatment of their advanced retinopathy. Posttransplant visual acuity improved at least more than one line in 56%, stabilized in 32%, and deteriorated in 12% of patients. Patients with functioning grafts for greater than 1 yr had no further deterioration of visual acuity. Vitreous hemorrhage frequency and severity dropped markedly from pretransplant (from 69 to 24%) 10 mo after grafting. Retinal morphology remained stable in all eyes except two.(ABSTRACT TRUNCATED AT 250 WORDS)