This study examined the effects of the lipophobic electron acceptor, nitroblue tetrazolium (2x5 micromol/kg, i.v.) on the vasodilation produced by the putative endothelium-derived S-nitrosothiol, L-S-nitrosocysteine (400 nmol/kg, i.v.), and the nitric oxide (NO) donor, (Z)-1-N-methyl-N-[6(N-methylammoniohexyl)amino]&z. sfnc;diazen-1-ium-1,2-diolate (MAHMA NONOate, 25 nmol/kg, i.v.), in anesthetized rats. The administration of nitroblue tetrazolium resulted in delayed but long-lasting increases in vascular resistances. The L-S-nitrosocysteine-induced vasodilator responses were markedly diminished whereas the MAHMA NONOate-induced responses were not affected by nitroblue tetrazolium. These results support the possibility that L-S-nitrosocysteine interacts with membrane thiols that are subject to nitroblue tetrazolium-induced oxidation (i.e., disulfide-bridge formation) and that nitroblue tetrazolium-induced vasoconstriction may involve a loss of potency of endothelium-derived S-nitrosothiols.