The Diabetes Control and Complications Trial demonstrated that intensive diabetes therapy effectively delays the onset of clinically apparent neuropathy in patients with insulin-dependent diabetes mellitus. A total of 1,441 patients with insulin-dependent diabetes mellitus were randomly assigned to receive intensive treatment or conventional treatment. Of these, 1,290 were randomized at least 41/2 years or more prior to study termination. Nerve conduction studies were performed at baseline and repeated after approximately 5 years for 1,243 of these patients, 96% of the eligible population. After 5 years of treatment, significant nerve conduction differences were observed between the intensive and conventional treatment groups, all favoring better performance (faster sensory and motor conduction velocities and shorter F-wave latencies) in the intensive treatment group. Moreover, while performance generally deteriorated among the conventionally treated patients, most attributes remained stable or showed modest improvement in the intensively treated group. Treatment group differences were consistent across strata defined by duration of diabetes and the presence of neuropathy at baseline. A nonparametric multivariate test of all ten nerve conduction measures established a strong effect in favor of intensive treatment. These data confirm that the electrophysiological abnormalities associated with diabetic neuropathy are delayed or prevented by intensive diabetes treatment.