Agmatine was about as potent as aminoguanidine to inhibit the activity of the inducible form of nitric oxide synthase (iNOS) in isolated rat aorta. Like aminoguanidine, agmatine was devoid of significant activity on the constitutive form of NOS. Agmatine inhibited the conversion of [3H]L-arginine in [3H]L-citrulline in partially purified iNOS from macrophages (IC50 = 262 +/- 39.9 microM). Thus, our data suggest that agmatine may act as endogenous inhibitor of iNOS.