Only recently, a heterozygous mouse model has been described with a reduced expression of mangan superoxide dismutase 2. The MnSOD knockout mice (MnSOD_KNO) are characterised by an increased oxidative stress in the heart. It has been proposed that this model is suitable to investigate age-dependent alterations in heart failure (Strassburger et al. 2005). We investigated the influence of physical exercise on cardiac function in male MnSOD knockout mice (MnSOD_KNO_EXER, n=11) and wildtype mice (WT_EXER, n=6). Animals were trained for 8 weeks on a running wheel (1h/day at 15 m/min for 5 days/week, angle: 5°). Controls were untrained animals (WT_CON, n=7; MnSOD_KNO_CON; n=9). Heart to body weight ratio was sig. increased in MnSOD_KNO independently from physical exercise. Under baseline conditions, left ventricular enddiastolic volume was ony increased in MnSOD_KNO_EXER and heart frequency (HF) was similar in all groups. In the hearts of WT_EXER, a significant increase in capillary density was observed, whereas no alterations in capillary density were observed in MnSOD_KNO_EXER.Conclusions: Physical exercise is able to induce a dilative cardiac phenotype under conditions of increased oxidative stress. Increased exposure to radicals seems to decrease exercise-induced angiogenesis.