During myocardial ischaemia the purine (ATP, GTP) and pyrimidine (CTP, UTP) nucleotide content of the myocyte falls. When the ischaemic episode resolves, many hours or even days are required for restoration of nucleotide pools. These observations suggest that repetitive episodes of ischaemia might produce progressive depletion of nucleotide pools. In order to determine the effect of repetitive episodes of brief ischaemia on nucleotide pools, open-chest dogs underwent three 12 min periods of occlusion of the left anterior descending coronary artery, with each occlusion followed by 10 min of reperfusion. During the first occlusion nucleotide pools decreased by 30% (ATP); 36% (GTP), 52% (CTP), and 48% (UTP). The subsequent two occlusions produced no further decrease in nucleotide pools. The myocardial content of adenine nucleotide catabolites (adenosine + inosine + hypoxanthine) tended to be greater during the first occlusion than during the subsequent occlusions, and substrate delivery (ie regional myocardial blood flow) was similar during each of the periods of ischaemia. These results indicate that a decrease in the rate of nucleotide degradation, rather than an increase in nucleotide synthesis, accounts for the maintenance of nucleotide content during subsequent ischaemic episodes after the initial ischaemic period. Thus repetitive episodes of regional ischaemia do not produce a cumulative decrease in the high energy phosphate content of the myocardium.