Previous studies have demonstrated that the positron-emitting fluorine-18 (18F)-labeled fluoromisonidazole is a specific tracer of myocardial hypoxia. Its fractional extraction Is enhanced in ischemic or hypoxic myocardium but returns to baseline levels on reperfusion and recovery of normal function. Thus, this agent might be useful in delineating acutely hypoxic but potentially salvageable myocardium. Accordingly, to delineate the relation between the myocardial extraction of 18F-fluoromisonidazole after intravenous administration and the time of antecedent ischemia in vivo, uptake of tracer was measured with positron emission tomography and direct postmortem tissue analysis in 14 dogs in which tracer was administered within 3 h of coronary occlusion (a time associated with marked potential for salvage on reperfusion); in 4 dogs after 6 h of coronary occlusion (a time associated with minimal salvage of myocardium on reperfusion); and in 8 dogs after > 24 h of coronary occlusion (to delineate uptake in tissue that is irreversibly damaged). The residual fraction (that is, the amount of tracer extracted and retained in a region) in ischemic myocardium in the dogs in which 18F-fluoromisonidazole was administered within 3 h after occlusion averaged (± standard deviation) 23 ± 18%, which was higher than the residual fraction in myocardium subjected to ischemia for either 6 or > 24 h before tracer administration (12 ± 7% and 5 ± 2%, respectively, p < 0.01 for both). Retention of tracer in remote normal myocardium averaged 2 ± 1%. Because marked enhancement of extraction of 18F-fluoromisonidazole occurred in myocardium only early after the ischemic insult, this agent may hold promise for the noninvasive identification of Jeopardized but salvageable myocardium. In addition, it should be useful in enhancing the understanding of the basic role of myocardial hypoxia in cardiac disease and its response to treatment.