Calcium channel blockers may prevent myocardial injury during cardioplegia and reperfusion. This study was done to evaluate the effects of diltiazem cardioplegia on myocardial protection during ischemic arrest and recovery of myocardial function after reperfusion. Four formulations of crystalloid cardioplegic solutions, GIK solution[group I, n=12], diltiazem[lug/ml GIK] in GIK solution[group II, n=7], ],diltiazem[2ug/ml GIK] in GIK solution[group III, n=6] and diltiazem[4ug/ml GIK] in GIK solution[group IV, n=6] were compared in isolated working rat heart subjected to a long period [2 hours] of hypothermic arrest with multi-dose infusion. Diltiazem cardioplegia[group II, III and IV]was found to be superior in nearly all aspects. Diltiazem cardioplegia showed faster recovery of regular rhythm and lower incidence of ventricular fibrillation than group I did. In comparing mechanical function in all experimental hearts, the mean postischemic recoveries of aortic flow, cardiac output, peak aortic pressure, stroke volume and stroke work[expressed as a percentage of its preischemic control] were significantly greater in group II, III and IV[diltiazem cardioplegia] than in group I. The infused amount of cardioplegic solution was more increased by the addition of diltiazem to GI K solution. [p < 0.01] Creatine kinase leakage tended to be lower in hearts receiving diltiazem cardioplegia, especially in group III and IV[p<0.05] than in those receiving GIK solution only[group I]. Diltiazem cardioplegia results in the increased flow of cardioplegic solution and the decreased ischemic injury of myocardium during ischemic arrest and the improved recovery of myocardial function after reperfusion, and a dose-response relation must be established before clinical use.