The sympathetic skin response (SSR), the quantitative sudomotor axon reflex test (Q-SART), and cardiac beat-to-beat variability with respiration as measured by the expiratory/inspiratory ratio (E/I ratio) were studied in 39 patients with diabetic neuropathy of whom 33 also had one or more symptoms of autonomic involvement. In the lower extremities 87% of the patients with an absent SSR had an abnormal Q-SART (P less than 0.001), and 81% of patients with the SSR present had a normal Q-SART (P less than 0.02). The E/I ratio was abnormal in all but one of 23 patients with an absent SSR in the foot, and a normal E/I ratio was present only in those patients (n = 7) with the SSR present in hand and foot, and in an eighth patient who had SSR absent in the foot and present in the hand. A similar correlation was found between the E/I ratio and the Q-SART in the foot, although 4 of 25 patients with an abnormal foot Q-SART had a normal E/I ratio. We conclude that the concordance of results of the SSR and Q-SART supports the combined use of these tests to uncover early distal sympathetic failure in diabetic neuropathy.