In the isolated, perfused working rat heart, ischemia (15 min) decreased mechanical function and also the tissue levels of ATP and creatine phosphate, and increased the tissue levels of lactate and free fatty acids including arachidonic acid. Reperfusion (20 min) did not restore mechanical function, but restored changes of metabolites incompletely except for free fatty acids, which changed further during reperfusion. Drugs were given 5 min before ischemia until the end of ischemia or for the first 10 min after reperfusion. Both dl- and d-propranolol (10 and 30 microM) decreased mechanical function, accelerated the recovery of mechanical function during reperfusion following ischemia, and attenuated ischemia reperfusion-induced metabolic changes. The attenuation of reperfusion-induced metabolic changes was more marked when these drugs were present during reperfusion. d-Propranolol showed a cardioprotection similar to that by dl-propranolol. Timolol (50 microM) did not accelerate the recovery of mechanical function during reperfusion, and did not attenuate the reperfusion-induced metabolic changes. These results suggest that d-propranolol, like dl-propranolol, has a cardioprotective effect which is probably due to its membrane stabilizing (or sodium channel blocking) action.