This study demonstrates that the decreases in hindquarter vascular resistance produced by the putative endothelium-derived S-nitrosothiol, l-S-nitrosocysteine, in urethane-anesthetized rats, were attenuated by a lower dose of the N-methyl-d-aspartate (NMDA) receptor ion-channel blocker, dizocilpine (MK-801, 200 μg/kg, i.v.), whereas they were augmented by a higher dose of dizocilpine (500 μg/kg, i.v.). In contrast, l-S-nitrosocysteine-induced decreases in mesenteric vascular resistance were not affected by either dose of dizocilpine. The vasodilator actions of l-S-nitrosocysteine in these beds were not affected by the competitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (2-AP5). The vasodilator actions of the nitric oxide (NO) donor, (Z)-1-∣N-methyl-N-[6(N-methylammoniohexyl)amino]∣diazen-1-ium-1,2-diolate (MAHMA NONOate), in these beds were not affected by dizocilpine or by 2-AP5. These findings suggest that l-S-nitrosocysteine recognition sites in hindquarter but not mesenteric beds may be associated with dizocilpine-sensitive ion-channels similar to those in NMDA receptors.