The effect of platelet-activating factor (PAF) was studied during the acute phase of myocardial ischemia in cats. PAF infusion (0.75 micrograms/kg/h for 4.5h) in anesthetized, open-chest cat decreased arterial blood pressure, but did not influence heart rate or biochemical indices of cell integrity. The same dose of PAF, however, started 30 min after coronary ligation, resulted in a significantly higher elevation of plasma creatine phosphokinase (CK) activity and a reduced CK content in the region of the ischemic myocardium. Treatment with the thromboxane A2 synthetase inhibitor, CGS-13080, significantly attenuated the PAF-aggravated ischemic cellular damage. These experiments suggest that hypoxia-generated PAF may contribute to the aggravation of myocardial ischemia, part of which appears to be due to PAF-induced release of thromboxane A2.