Diabetic polyneuropathy is a common, disabling chronic complication of diabetes mellitus. Previous studies have suggested that combined pancreas-kidney transplantation can ameliorate nerve conduction. The relative contribution of the correction of hyperglycaemia and uraemia on nerve function is still a matter of debate. Nerve conduction velocity (NCV) was assessed before and after simultaneous pancreas and kidney transplantation, and before and after pancreas graft failure in five insulin-dependent diabetic (IDDM) patients affected by severe diabetic polyneuropathy. Sensory and motor NCV were recorded in five nerves and expressed as a cumulative index for each patient. Metabolic control was evaluated by fasting blood glucose and glycosylated haemoglobin levels. NCV index was below normal values before transplant: -3.8 +/- 0.7 (normal value: 0.89), improved 1 and 2 years after transplant: -3.1 +/- 1.3 and -2.6 +/- 0.9 (p = 0.0019), stabilised until pancreas failure and deteriorated to pre-transplant values 2 years after pancreas graft failure: -3.6 +/- 1.0 (p = 0.034). Fasting blood glucose levels worsened after pancreas graft failure. HbA1c levels, in the normal range during functioning pancreas graft (6.6 +/- 0.6%), deteriorated after its failure (8.0 +/- 0.6%, p = 0.04). Kidney function was preserved. These data support a positive effect of pancreas transplantation per se on NCV in IDDM subjects with diabetic polyneuropathy, thus demonstrating that metabolic control provided by a self-regulated source of insulin not only halts but also ameliorates nerve function, even if polyneuropathy is advanced.