To delineate beneficial effects of intracoronary thrombolysis on myocardial metabolism In vivo and their dependence on the interval after coronary occlusion prior to reperfusion, we studied 23 closed-chest dogs. Coronary occlusion was produced with a thrombogenic copper coil prior to performance of cardiac positron emission tomography with 11C-palmitate. Jeopardized zones were calculated by summation of myocardial regions exhibiting less than 50 percent of the peak left ventricular wall radioactivity, and residual metabolic activity within jeoparized zones quantified based on the average counts compared with average counts in normal myocardium. After tomography, streptokinase was infused into the coronary artery (4,000 units per minute), resulting in anglographically demonstrable restoration of patency. Repeat tomography performed 90 minutes after the initial study with a second injection of 11C-palmitmate demonstrated reduction of jeopardized zones by 51 ± 6.3 percent (SE) and by 21 ± 1.8 (p < 0.01 based on paired comparisons) when refusion was initiated 1 to 2 (in four dogs) or 2 to 4 (in six dogs) hours after occlusion. Metabolic activity in initially jeoparidized regions increased by 111 ± 24.3 percent and 61.8 ± 12.6 (p < 0.01 for each). When streptokinase was infused later after occlusion, significant salutary metabolic effects did not occur. These results indicate that positron tomography may be useful in the clinical delineation of the efficacy of thrombolytic therapy in restoring myocardial metabolism and underscore the marked dependence of such efficacy on the duration of the interval of ischemia prior to the onset of reperfusion.