To determine the value of lactate and the adenosine metabolites inosine and hypoxanthine as indicators of myocardial ischemia, we measured the levels of these metabolites in arterial and coronary sinus blood of nine chronically instrumented dogs subjected to exercise stress before and during reversible circumflex coronary artery occlusion. The degree of circumflex bed hypoperfusion was measured by 15-μ microspheres and the reduction in circumflex coronary flow was measured wth a proximal flow probe. Adenosine metabolites, although below the level of accurate detection on our laboratory in arterial blood (i.e. 0.5 μM/l), were detected in coronary sinus blood (range 2.7-18.7 μM/l) in 26 of 33 studies wth partial circumflex occlusion when circumflex flow was reduced to less than 80% of that seen during exercise without occlusion and when only subendocardial perfusion was reduced. Global left ventricular flow and transmural flow in nonischemic beds did not correlate with positive studies. Myocardial lactate extraction was a less accurate test for determining curcumflex bed hypoperfusion. Thus, myocardial production of adenosine metabolites is a sensitive qualitative test of exercise-induced ischemia responding to a modest fall in coronary flow when only subendocardial hypoperfusion is present.