Cardiac prostaglandin release was studied in closed-chest dogs during acute coronary occlusion. Aortic and coronary sinus blood was obtained before, and at intervals after, balloon occlusion of the left anterior descending artery in 7 dogs. Samples were assayed for PGF [prostaglandin F], PGE and PGA by radioimmunoassay. All dogs demonstrated PGF release. Mean .+-. SE postooclusion aortic levels were 0.26 .+-. 0.01 ng/ml and coronary sinus levels were 0.67 .+-. 0.01 ng/ml (P < 0.001). In 6 dogs, PGE also was released. Mean postocclusion aortic levels were 0.24 .+-. 0.01 ng/ml; and coronary sinus, 0.44 .+-. 0.01 ng/ml (P < 0.001). There was no release of PGA. To examine the site of PG release, simultaneous samples from the aorta, the coronary sinus and the great cardiac vein were obtained before and after left circumflex artery occlusion in 6 additional studies. The great cardiac vein drained effluent from nonischemic myocardium, whereas the coronary sinus drainage included blood from both ischemic and nonischemic zones. All 6 dogs demonstrated PGF release from the ischemic region. Mean postocclusion aortic PGF was 0.32 .+-. 0.01 ng/ml. Coronary sinus PGF was 1.69 .+-. 0.03 ng/ml (P < 0.001), whereas the great cardiac vein level remained at 0.34 .+-. 0.01 ng/ml (P > 0.05). PGE was released from both ischemic and nonischemic regions. Mean aortic PGE was 0.21 .+-. 0.01 ng/ml; great cardiac vein, 0.55 .+-. 0.02 ng/ml (P < 0.001); and coronary sinus, 1.07 .+-. 0.04 ng/ml (P < 0.001). The different local availability of PGE and PGF may influence the cardiac response to ischemia.