Coronary autoregulation appears to be closely coupled to myocardial oxidative metabolism. Recent data suggest that coronary autoregulation depends on the prevailing balance between myocardial oxygen supply and demand. It seems likely that pO2 within a critical range may be the initial metabolic stimulus for coronary autoregulation. Whether adjustments in vascular resistance result from changes in myocardial pO2 directly or indirectly through changes in vasoactive metabolites remains unclear. The observation that intracoronary infusion of adenosine deaminase in concentrations sufficient to attenuate myocardial reactive hyperemia has no effect on coronary autoregulation strongly suggests that adenosine is not essential for autoregulation in the blood-perfused dog heart. This is supported by the recent finding that the interstitial concentration of adenosine (estimated from epicardial exudate) remained unchanged during autoregulation. Prostaglandins may play a role in autoregulation in buffer-perfused rabbit hearts but do not appear to be involved in blood-perfused dog hearts. Potassium is probably not involved in autoregulation. It is also unlikely that changes in tissue pressure can account for coronary autoregulation. The role of adenine nucleotides, hydrogen ion, carbon dioxide, and intermediate metabolites of the citric acid cycle, in coronary autoregulation has not been examined. The possibility that a myogenic mechanism contributes to coronary autoregulation has not been directly tested. Finally, it is entirely possible that coronary autoregulation may result from the concerted interaction of several different mediators or mechanisms. In this regard, it should be emphasized that blocking or destroying one mediator could elicit a compensatory increase in the contribution of another.