The muscarinic receptors of human eccrine sweat gland may be directly stimulated by iontophoresis of acetylcholine (direct response; DIR) and indirectly via nicotinic receptors and an axon "reflex" (AXR). Using a specially designed multicompartmental sweat cell and dual sudorometers, we were able to simultaneously record the evoked DIR and AXR responses. On a second day, we repeated the experiment under identical ambient and stimulus conditions but instead obtained silastic imprints of DIR and AXR for morphometry. Studies were done on 24 controls (mean +/- SD = 47.6 +/- 15.1 years) and 23 diabetic subjects (mean +/- SD = 49.6 +/- 16.3 years). In control subjects, sudorometric DIR recordings were consistently larger than AXR. There was no difference in sweat droplet density by sex, but the size of droplets was larger in males. In diabetic patients 3 of 23 had absent AXR but preserved DIR, suggesting that failure of AXR preceded DIR in patients with neuropathy. Patients with mild neuropathy had an overrepresentation of large diameter droplets in the silastic imprints of both DIR and AXR, while patients with severe neuropathy had a markedly reduced density and small diameter droplets.