The effects of histamine were analysed on human subcutaneous small arteries. No effect was seen on non-precontracted preparations. After precontraction (norepinephrine 1 μM and K + 30 mM) histamine potently relaxed the arteries (EC 5 0 =0.3 μM; max. effect=95% relaxation). The histamine H 1 receptor antagonist, pyrilamine (10 μM), had only a small, non-significant inhibitory influence on histamine-induced relaxation while the histamine H 2 receptor antagonist, cimetidine (0.1 mM), had a significant inhibitory influence. Relaxation was completely blocked in the presence of both antagonists. Both 2-pyridylethylamine (histamine H 1 receptor agonist) and dimaprit (histamine H 2 receptor agonist) elicited relaxation. Removal of endothelium reduced the relaxation effects of histamine and 2-pyridylethylamine, but not of dimaprit. Inhibition of nitric oxide synthesis by nitro-l-arginine significantly inhibited histamine-induced relaxation and even more clearly the cimetidine-resistant component. We conclude that histamine potently relaxes human subcutaneous arterioles, and that most probably both muscular histamine H 2 receptors and endothelial histamine H 1 receptors, thus activating nitric oxide release, contribute to the relaxation.