The isolated perfused rabbit heart has the capacity to rapidly synthesize, release, and inactivate prostaglandins (PGs) which can readily modulate coronary resistance and cardiac performance. Prostaglandin synthetase converts arachidonic acid to prostaglandin-like substance in one passage across the heart. There is little evidence of functional prostaglandin dehydrogenase activity. Arachidonic acid and bradykinin produce a concentration-dependent decrease in coronary resistance directly associated with PG-like substance biosynthesis and release. An inhibitor of bradykinin destruction, the nonapeptide SQ-20881, markedly enhanced both the coronary vasodilation and PG-like substance release produced by cardiac injection of bradykinin. Indomethacin inhibited both the myocardial prostaglandin biosynthesis and the decrease in coronary resistance induced by bradykinin and arachidonic acid. In addition to direct effects on coronary vascular smooth muscle, prostaglandins produced in the heart apparently exert a modulating influence on efferent autonomic and on afferent cardiovascular and pain reflexes.