PostC modifies post-ischemic intracellular pH, activity of enzymes and redox-environment. We studied the role of acidosis on endogenous CAT and SOD activity in early (7 min) and late (120 min) phases of reperfusion (R). We measured protein levels of SOD and CAT, and the levels of 3-nitrotyrosine (3N) and S-nitrosylated (SN) proteins as indices of redox-environment. Isolated rat hearts were exposed to 30-min ischemia (I)/120-min R (I/R) only, PostC (5 cycles of 10-s at the beginning of 120-min R) or acidotic buffer (AB, pH = 6.6) during the initial 3 min of R, with or without exogenous-CAT (100U/ml) or -SOD (10U/ml). We measured ventricular pressure, infarct-size and LDH release. Activity of endogenous-CAT decreased and that of -SOD increased after I/R. Either PostC or AB inverted these effects on enzyme activities, both in early and late phase of R. PostC also reduced 3N and increased SN proteins in early R. Three min exogenous-SOD, but not -CAT infusion abolished both PostC- and AB-induced protection. In late R, Cu-SOD protein levels are decreased by I/R, but kept to control levels by PostC; Mn-SOD and CAT levels tend to decrease in I/R, and to increase after PostC or AB. Down-regulation of endogenous-SOD and up-regulation of endogenous-CAT activity may contribute to PostC- and AB-triggering of protection. Exogenous-SOD, but not -CAT, interferes with cardioprotection-triggering. Yet, PostC reduces 3N levels and favors SN, thus preventing further cellular oxidative stress.