The purpose of this study was to determine if differences in the cardioprotective abilities of ibuprofen and indomethacin were due to their differing abilities to alter the O2 supply/consumption ratio in the ischemic myocardium. Experiments were done on 21 anesthetized open-chest rabbits. Regional flow (using radioactive microspheres), O2 extraction, O2 consumption, and O2 supply/consumption ratio were determined 1 hr after occlusion of the left anterior descending coronary artery in controls and animals given iv 10 mg/kg ibuprofen or iv 3 mg/kg indomethacin. Myocardial blood flow was depressed in the occluded region compared to the nonoccluded region after occlusion for all treatments. O2 extraction in the occluded region was elevated compared to the nonoccluded region for all treatments after occlusion. No differences in O2 consumption were noted between any treatment within the occluded or nonoccluded regions. The O2 supply/consumption ratio was lower in the occluded region compared to the nonoccluded region for all treatments. No differences in this ratio were noted between any treatment. Thus, the effects of indomethacin or ibuprofen on ischemia are not related to acute changes in myocardial O2 supply/consumption balance.