The effect of lidocaine on the hydrogen peroxide (H2O2)-induced mechanical and metabolic changes was studied in the Langendorff rat heart, which was perfused aerobically at a constant flow rate and paced electrically. H2O2 (600 microM) increased the left ventricular end-diastolic pressure (i.e., mechanical dysfunction), decreased the tissue levels of ATP and creatine phosphate (i.e., metabolic change), and increased the tissue level of malondialdehyde (MDA). The mechanical and metabolic alterations induced by H2O2 were attenuated by lidocaine (50 or 200 microM). Lidocaine also attenuated the H2O2-induced increase in MDA. Nevertheless, lidocaine modified neither the myocardial ferrylmyoglobin level that was increased by H2O2 nor the H2O2 concentration in vitro and did not affect the mechanical function and energy metabolism of the normal heart. These results suggest that lidocaine attenuates both mechanical and metabolic changes induced by exogenous H2O2. The protective action of lidocaine on the H2O2-induced changes is due to neither energy-sparing nor H2O2-scavenging effect, but probably due to its effect to reduce the H2O2-induced lipid peroxidation.