The relation between myocardial release of prostaglandin and myocardial ischemia was studied in 12 selected patients with multivessel coronary artery disease. These 12 were chosen for analysis because they experienced angina pectoris, ischemic electrocardiographic changes and decreased myocardial lactate uptake during atrial pacing. Simultaneous aortic and coronary sinus blood samples were obtained at rest, during angina and after recovery and were assayed for prostaglandins F, E and A with radioimmunoassay. Cardiac release of prostaglandin F was observed during angina in 11 of 12 patients. Aortic prostaglandin levels remained constant throught each study. During angina, the mean aortovenous difference (+/- standard error) was -0.30 +/- 0.04 ng/ml (P less than 0.001) for prostaglandin F and -0.10 +/- 0.03 ng/ml (Pless than 0.001) for prostaglandin E. There was no significant release of prostaglandin A. Blood samples were also drawn at subanginal heart rates in two patients. Prostaglandin F was released only during angina. In three control patients with a chest pain syndrome and normal coronary arteries, comparable atrial pacing produced no release of prostaglandin F, E or A. These results, together with the known vascular and metabolic actions of prostaglandins, suggest that these pharmacologically active compounds may also play a physiologic role in the cardiac response to ischemia in man.