The present study was undertaken to elucidate a possible role of non-beta-receptor mediated effects in dl-propranolol-induced enhancement of post-hypoxic contractile and metabolic recovery in perfused rat hearts. The rat hearts were perfused for 30 min under reoxygenated conditions following 15 min-substrate free-hypoxic perfusion, and the cardiac performance and myocardial metabolism were examined. Hypoxia induced complete cessation of cardiac contractile force, depletion of myocardial high-energy phosphates, release of ATP metabolites and creatine kinase from the heart. Subsequent reoxygenation produced little recovery of cardiac contractile activity and tissue high-energy phosphates, further enhancement of the release of creatine kinase and the accumulation of tissue calcium. Treatment of the hypoxic hearts with dl-propranolol, d-propranolol and atenolol was performed during 5 to 15 min of hypoxic perfusion. dl-Propranolol and d-propranolol at the concentration of 45 microM elicited a significant recovery of cardiac contractile activity and restoration of myocardial high-energy phosphates. This treatment also resulted in a suppression of the release of creatine kinase and ATP metabolites and the tissue calcium accumulation observed during hypoxia and/or reoxygenation. However, such beneficial effects were not seen in hearts treated with 45 microM atenolol. dl-Propranolol and atenolol, but not d-propranolol, in a concentration of 45 microM have been shown to reveal beta-adrenoceptor blocking action. Thus, the results suggest the involvement of non-beta-receptor mediated effects of propranolol in the enhanced post-hypoxic contractile and metabolic recovery of the perfused rat heart. The non-beta-receptor mediated activity of these drugs appears to be related to their ability to suppress the maximal driving frequency of left atrial preparations.