Oxygen radical-mediated injury has been implicated in the process of cardiac aging. We investigated the tolerance to oxidative stress of hearts from rats of different age. Langendorff-perfused hearts from 3-12-month-old rats received a 30 min infusion of the reactive oxygen specie hydrogen peroxide (H2O2, 60 microM), followed by a 15 min wash-out. H2O2 infusion resulted in a significantly larger increase in end-diastolic pressure in hearts of 6- and 12-month-old rats than 3 months (P<0.01). In addition, developed pressure and rate-pressure product decreased more evidently in 12-month-old hearts (P<0.01 vs 3 and 6 months). Arrhythmia analysis showed higher score in hearts of 12- and 6-month-old rats with respect to 3-month-old animals (P<0.05). Cardiac release of oxidized glutathione (an index of the ability of the heart to inactivate oxygen metabolites) was significantly lower in hearts from rats of 6 and 12 months than in younger animals (P<0.001). Finally, cardiac concentrations of the scavenger enzymes glutathione peroxidase and Mn-superoxide dismutase also significantly decreased with age. In conclusion, in rat heart metabolic and functional tolerance toward oxidative stress decreases with age. This phenomenon may contribute to the development of cardiovascular alterations with increasing age.