Disturbances of neurovascular function in the extremities may occur in patients with diabetes mellitus, exposure to toxic substances and chronic exposure to vibrating hand tools, as well as in Raynaud's phenomena. In these conditions symptoms of paraesthesia, finger numbness and blanching occur, so nerve conduction studies, vibration and temperature threshold measurements and neurovascular function tests are used for objective assessment of neurological dysfunction. The aim of the present study was to examine some factors which may confound quantitative neuro-vascular function measurements if used to assess neuropathy in diabetics. All subjects were consenting volunteers without exposure to known neurotoxic chemicals. The 5 groups were (a) healthy non-diabetic subjects not exposed to vibration (n = 10, mean age 52.3 yrs) (b) 2 insulin dependent and 8 non-insulin dependent diabetic subjects with a mean of 6 years treatment (n = 10, mean age 55.7 yrs) (c) maintenance employees exposed to high frequency pneumatic hand tools (n = 10, mean age 52.2 yrs) (d) subjects who were not diabetic or exposed to vibrating tools, but were being treated with the ACE-inhibitor enalapril 20 mg daily for hypertension (n = 5, mean age 54 yrs) (e) subjects who had smoked more than 10 cigarettes daily for at least 15 yrs (n = 10, mean age 51 yrs). Neurovascular tests included axon reflex responses measured by laser Doppler velocimeter evoked on the dorsum of the finger by iontophoresis of acetylcholine 16 mC in a circumferential chamber: cutaneous microvascular dilator responses to endothelial stimulation by iontophoretic application of the muscarinic agonist pilocarpine 16 mC and to direct nitrodilator sodium nitroprusside 16 mC. The skin temperature of the digits was held between 33 degrees and 34 degrees C during testing and dilator responses were measured as flux change by on-line computer analysis using 'Perisoft'. There was a significant reduction (P < 0.05) in the neurovascular responses of both diabetics and vibration--exposed subjects to acetylcholine and, in the case of vibration-exposed subjects, to pilocarpine, but nitroprusside responses were not significantly different. Our findings of reductions in neurovascular responses in diabetics and in subjects exposed to higher frequency vibration is consistent with recent epidemiological findings. Furthermore, subjects treated with an ACE-inhibitor (enalapril) showed significant reduction in acetylcholine-evoked axon reflex responses, while the test group of smokers showed a significant reduction in their dilator response to pilocarpine.(ABSTRACT TRUNCATED AT 400 WORDS)