Pancreas transplantation prevents or retards development of early diabetic glomerular lesions in renal allografts transplanted to patients with insulin-dependent diabetes mellitus (IDDM), but its effect on established renal lesions in native kidneys of such patients is unknown. Renal biopsy samples were taken before and 5 years after pancreas transplantation from 13 non-uraemic IDDM patients and compared with baseline and 5-year biopsy samples from 10 persistently hyperglycaemic IDDM patients who did not undergo transplantation. The two groups were similar in age, duration of diabetes, metabolic control, renal function, and blood pressure. Glomerular structures were measured by standard morphometric techniques. Haemoglobin A1 concentrations fell to within the normal range after pancreas transplantation but did not change in the comparison group. Glomerular basement membrane width did not significantly change in either group. Glomerular volume decreased and mesangial fractional volume increased in the pancreas transplant recipients but there was no significant change in total mesangial volume over 5 years. By contrast, both glomerular volume and mesangial fractional volume increased in the comparison patients, resulting in increased total mesangial volume. Diabetic glomerular lesions in patients with their own kidneys were not ameliorated by pancreas transplantation, despite 5 years of normoglycaemia. Pancreas transplantation can correct severe metabolic instability and thus improve quality of life, but it cannot yet be recommended for the treatment of established lesions of diabetic nephropathy.