Twenty-four mice (male, 8 weeks) were divided equally into four groups: Control (GC), Amphetamine (GAnf), Exercise (GEx) and Exercise with Amphetamine (GExAnf). The protocol began with i.p. administration of 0.1 ml saline solution (to GC and GEx) and 20 mg/kg d-amphetamine dissolved in 0.1 ml saline solution (to GAnf and GExAnf). Immediately afterwards, GEx and GExAnf started exercise (swimming, 60 min at 37 degrtees C). At the same time GC and GAnf were immersed in shallow water (60 min at 37 degrees C, without exercise). Subcutaneous temperature was measured every 15 minutes, and the animals were sacrificed 60 min after the i.p. injection, with cardiac muscle tissue harvested for histological analysis and quantification of oxidized and reduced glutathione (GSSG and GSH), thiobarbituric acid reactive substances (TBARS) and carbonyl groups. Body temperature remained constant during the protocol, in all groups. GC and GEx exhibited normal histology, whereas GAnf exhibited the most marked histological changes. GSH levels were higher (p < 0.05) in GEx and GExAnf (vs. GC and GAnf respectively) with similar % GSSG in all groups. TBARS content was also similar in all groups; carbonyl groups were higher (p < 0.05) in GEx (122 +/- 7) and GExAnf (129 +/- 9) compared to GC (100 +/-7 ) and GAnf (114 +/-7). Carbonyl group levels were significantly higher in GAnf than in GC. Administration of 20 mg/kg of d-amphetamine produced histological signs of cardiotoxicity, which were not enhanced by physical exercise; however, the combined action of d-amphetamine and physical exercise significantly aggravated protein oxidation markers.