The efficacy of blood and crystalloid retrograde cardioplegia in protecting the ischemic myocardium was compared. Seventeen dogs underwent 2 hr of global myocardial ischemia while on cardiopulmonary bypass. Crystalloid (in nine dogs) or blood (in eight dogs) cardioplegic solution was infused continuously into the coronary sinus. Left and right ventricular function were assessed before ischemia and after 30 and 60 min of reperfusion by means of highly sensitive, load-independent index of contractility (the slope of the stroke work vs end-diastolic length relationship). Ventricular biopsies for ATP determination were obtained before ischemia, at the end of ischemia, and after 60 min of reperfusion. Left and right ventricular function returned to normal after 60 min of reperfusion in both groups. Left ventricular ATP remained unchanged, whereas small but significant decreases in right ventricular ATP were observed after 60 min of reperfusion in both groups. Thus continuous crystalloid or blood retrograde coronary sinus cardioplegia in dogs preserved myocardial function and metabolism equally well after 2 hr of global cardiac ischemia.