Isolated rat hearts were subjected to retrograde perfusion to investigate the protective effects of adenosine and verapamil on the myocardium. In group 1, the perfusate was standard Krebs-Henseleit buffer solution. The perfusate was changed to Krebs-Henseleit buffer containing verapamil (100 nM) in group 2, adenosine (100 microM) in group 3 and both drugs in combination in group 4 for 30 min before ischemia and during 20 min of reperfusion. Group 2 displayed a recovery of creatine phosphate but not of ATP at the end of reperfusion. In group 4, the recovery of both ATP and creatine phosphate was significantly greater than in group 1. The coronary flow of group 4 was significantly higher than that of the other groups. Treatment with both verapamil and adenosine before and after global ischemia may protect the ischemic myocardium by improving high energy phosphate metabolism and coronary circulation.