Myocardial ischemia and reperfusion result in endothelial and ventricular dysfunction. Beta-blockers protect the myocytes from injury by acting as anti-ischemia agents. These anti-ischemic effects of the beta-blockers are due not only to their negative inotropic/chronotropic effects but also to a lipid peroxidation reducing mechanism. Thus, beta-blockers enhance myocardial recovery. In the present study 20 isolated guinea-pig hearts were perfused with Krebs-Henseleit buffer (KHB) using a Langendorff apparatus. The animals were allocated into 2 groups. In the study group (Group I), metoprolol, as the beta-blocker agent, was added into the KHB and in the control group (Group II) perfusion was performed without metoprolol. The percentage change (%change) of heart rate, developed pressure and dP/dtmax; malondialdehyde (MDA) and glutathione (GSH) levels of the perfusate and heart tissue were obtained as data. The %change of heart rate was 70.5+/-9.2 in the study group and 87.3+/-8.2 in the control (p=0.003). The %change of developed pressure was 68.7+/-14.4 and 55.9+/-8.6 in the study group and control group, respectively (p=0.04). The % change of dP/dt was 63.3+/-10.0 in the study group and 54.4+/-5.3 in the control group (p=0.01). The tissue MDA level was 31.0+/-5.5 nmol/g tissue in the study group and 53.5+/-4.2 nmol/g tissue in the control group (p=0.0002). The tissue GSH levels were 1.08+/-0.20 and 0.80+/-0.07 (mol/g tissue) in Groups I and TI, respectively (p=0.001). The levels of the perfusate MDA decreased and the levels of the perfusate GSH increased significantly in the metoprolol group in the postreperfusion period in comparison with the preischemia term (p=0.003 and p=0.03, respectively). Metoprolol reduces ischemic injury via prevention of lipid peroxidation and reduces the myocardial energy demand by decreasing the heart rate.