The sympathetic skin response (SSR) was studied in 47 diabetic patients selected for the presence of symptoms and clinical signs of peripheral neuropathy and in 24 normal control subjects. The SSR was present in all controls but was absent at the foot in 66% and at the hand in 27.7% of the diabetic patients. Absence of the SSR failed to correlate with other electrophysiologic parameters on routine nerve conduction and electromyographic studies. Although absent SSR was more often found in patients with symptoms of autonomic dysfunction (P less than 0.05), there was no correlation with any specific symptoms of autonomic involvement. The SSR was frequently absent, at least in the foot, in those patients with abnormal cardiac beat-to-beat variability (expiratory: inspiratory, E:I, ratio) and pupil cycle time (PCT). In addition there was a good correlation between the amplitude of the SSR and the value of the E:I ratio (r = 0.81, P less than 0.001). The SSR may be a valuable adjunct in the assessment of autonomic involvement in diabetic neuropathy, but its sensitivity requires further evaluation.