Thirty-five isolated hearts from newborn rabbits (aged birth to 2 days) were subjected to 120 minutes of ischemia at 15 degrees C with high potassium crystalloid cardioplegia. They were divided into four groups according to the method of cardioplegic administration: group C (preischemic control, n = 9), group S (single dose, n = 10), group M-1 (multiple dose, infused every 40 minutes, n = 7), and group M-2 (multiple dose, infused every 20 minutes, n = 9). After 30 minutes of reperfusion, the heart rate, coronary flow, creatine kinase release, percent water content, and myocardial ultrastructural scores for mitochondrial damage and intracellular edema were compared among the four groups. All of these parameters except coronary flow were significantly poorer in group M-2 than in groups C and S (p less than 0.05). The mitochondrial damage and intracellular edema scores were significantly poorer in group M-1 than in group C (p less than 0.05). No significant differences in these two scores were seen between group S and group C and between group S and group M-1. These results indicate that the single dose method of administering crystalloid cardioplegia may provide better myocardial protection than the multiple dose method in the neonate.