The calcium channel blocker, diltiazem, has been studied in the same model used for evaluation of cold blood-potassium cardioplegia. Six dogs (Group 1) had one hour of myocardial ischemia with topical ice (myocardial temperature, 7 degrees +/- 2 degrees C) after coronary perfusion with 200 ml of cold blood (5 degrees +/- 1 degree C) containing diltiazem, 400 micrograms per kilogram of body weight. Seven dogs (Group 2) had two hours of ischemia after perfusion with 200 ml of cold blood containing 200 micrograms/kg and reperfusion every 30 minutes with 100 ml of cold blood and diltiazem, 100 micrograms/kg. Baseline studies were repeated after rewarming and 40 minutes of reperfusion. No inotropic agents or calcium were used. Heart rate, peak systolic pressure, velocity of the contractile element, peak + rate of rise of left ventricular pressure (dP/dt), peak - dP/dt, dP/dt over common peak isovolumic pressure, left ventricular compliance and stiffness, and heart water were unchanged in Group 1. In Group 2, heart rate slowed (p less than 0.025) and compliance decreased (p less than 0.02). In both groups, coronary vascular resistance declined (p less than 0.001) and recovery of adenosine triphosphate (p less than 0.001), adenosine diphosphate (p less than 0.025), and the adenosine pool (p less than 0.001) was impaired. Ultrastructure was well preserved, but myofibrillar lesions were noted in Group 2. Diltiazem cardioplegia was associated with good functional recovery, but there was impairment of high-energy phosphate metabolism.