A B S T R A CT Experiments were performed to evaluate the role of prostaglandin synthesis in the regulation of coronary blood flow in dog hearts. The left main coronary artery was cannulated and flow measured both in otherwise intact animals and in canine heart-lung preparations. Prostaglandin E was measured by radioimmunoassay. Reactive hyperemia (flow after occlusion release) was induced by coronary occlusion for 10, 15, and 20 s and was 39±13 (mean±SEM), 66+21, and 82±24 ml, respectively. Indomethacin, an inhibitor of prostaglandin synthetase, reduced reactive hyperemia at 10, 15, and 20 s to 15-+-5, 33+11, and 47+17 ml, respectively (P <0.05). Meclofenamate, a different prostaglandin synthetase inhibitor, gave similar results. In a second group of five dogs, prostaglandin production of the heart was examined in response to 20-s occlusions.There wvas a significant increase in prostaglandin production from a basal level of 18.6±4.9 ng/min to 35.3+ 5.8 ng/min after occlusion of the coronary artery for 20 s (P < 0.05). After indomethacin, this increase in prostaglandin production was not observed and reactive hyperemia was significantly reduced. Thus, prostaglandin synthesis appears to be important in modulating canine coronary blood flow in response to brief periods of coronary occlusion.