THE acute action of insulin on neurogenic flare was investigated using iontophoresis. Twenty-five patients with insulin-dependent diabetes mellitus (IDDM) and 25 age- and gender-matched controls were studied. Axon reflex vasodilatation was evoked by transdermal iontophoresis of acetylcholine (ACh) before and after skin treatment by the iontophoresis of insulin and measured using laser Doppler velocimetry. Axon reflex responses were reduced in IDDM patients compared with controls (p< 0.001) but were restored after the iontophoresis of insulin. Insulin iontophoresis had no effect on the size of the axon reflex response in control subjects (p< 0.05). This study confirms the reduction of the ACh-induced flare in human patients with IDDM and has demonstrated relatively rapid effects of insulin on this cutaneous neurogenic response.