OBJECTIVE The aim of the study was to compare peripheral sympathetic adrenergic and cholinergic nerve function in NIDDM (non-insulin-dependent diabetes mellitus) patients with various degrees of diabetic neuropathy and neuropathic foot ulceration. The parameters used were postural vasoconstriction arteriolar reflex (VAR) and sympathetic skin response (SSR), respectively. METHODS Forty-seven NIDDM patients were studied. No patients had clinically significant peripheral vascular disease. They were divided according to peripheral somatic neuropathy, assessed by clinical score and vibration perception threshold (VPT). Twenty-two patients showed no significant evidence of peripheral neuropathy and normal VPT (DN-); 15 had signs and symptoms of neuropathy and VPT alteration (DN+); 10 had diabetic neuropathy and foot ulceration (DNU). Twenty-two normal subjects were also examined as a control group. Resting arteriovenous shunt skin blood flow, measured using laser-Doppler flowmetry, and the VAR of the big toe on lowering the foot were studied. Sympathetic skin response was assessed by an EMG apparatus. Autonomic function was also investigated by using standard cardiovascular reflex tests. RESULTS Resting blood flow values were similar in the three NIDDM groups and in the control group. VAR to foot lowering was significantly impaired in all NIDDM groups by comparison with controls (72.8 +/- 2.1%, mean +/- SEM), this impairment being progressively more pronounced in DN- (58.8 +/- 2.3%, P < 0.001), DN+ (33.3 +/- 3.0%, P < 0.001 versus DN-) and DNU (8.6 +/- 2.7%, P < 0.001 versus DN+). Sympathetic skin response was assessed in 28 patients and was significantly impaired in DN-compared with the control group (2.53 +/- 0.04 versus 2.71 +/- 0.04 log mcV, P < 0.01). This impairment was severe in the DNU compared with the DN+ group (1.36 +/- 0.05 versus 2.26 +/- 0.04 log mcV, P < 0.005). A positive correlation was found between VAR values and SSR (P < 0.001), and these measurements were also closely correlated with several parameters of central autonomic and somatic neuropathy. CONCLUSIONS These results indicate that peripheral sympathetic adrenergic and cholinergic fibers simultaneously undergo early alterations in diabetic patients, even when there is no clinical neuropathy. Our data also show almost complete abolition of peripheral sympathetic activity in NIDDM patients with foot ulceration.