The nitric oxide (NO)-dependent S-nitrosation of thiols to generate S-nitrosothiols has been proposed as an important pathway for the metabolism of NO in vivo, Although it has been suggested that these S-nitrosated compounds are resistant to decomposition by reactive oxygen metabolites (ROMs), very little information is available regarding the interaction between S-nitrosothiols and ROMs. We found that S-nitrosoglutathione (GSNO) rapidly reacted with O-2(-) to generate glutathione disulfide and equimolar quantities of nitrite and nitrate, The reaction was second order with respect of GSNO and first order with respect of O-2(-) with a rate equation of -d[GSNO]/dt = 2k(3)[GSNO](2)[O-2(-)], where k(3) = 3 - 6x10(8) M(-2)s(-1), I, addition, the reaction of GSNO with O-2(-) generated a strong oxidant as an intermediate capable of oxidizing dihydrorhodamine in the absence of the apparent generation of NO, We conclude that O-2(-) may act as a physiological modulator of S-nitrosation reactions by directly promoting the decomposition of S-nitrosothiols. (C) 1998 Academic Press.