The effect of L-arginine on isolated human uterine artery rings was investigated. L-Arginine, but not D-arginine, induced concentration-dependent relaxation. Removal of the endothelium enhanced the relaxant effects of L-arginine. Methylene blue and dexamethasone non-competitively inhibited L-arginine-induced relaxation, while NG-monomethyl-L-arginine competitively antagonized the response to L-arginine. Calmidazolium did not affect relaxation evoked by L-arginine. The dissociation constants obtained for L-arginine and NG-monomethyl-L-arginine in intact rings were not significantly different from those in endothelium-denuded rings. It is concluded that the relaxation induced by L-arginine in human uterine artery is mediated by non-endothelial nitric oxide production. We suggest that the NO synthase mediating the L-arginine-induced relaxation is an inducible type.