The tissue uptake and distribution of <sup>3</sup>H-dexamethasone were studied in anesthetized cats subjected to acute myocardial ischemia. 1 h after injection of <sup>3</sup>H-dexamethasone, liver, kidney, intestine, pancreas and heart exhibited tissue/plasma ratios between 2 and 7. Adrenal, spleen and lung tissue exhibited T/P ratios from 1 to 2, while ratios less than 1 were found in abdominal aorta, skeletal muscle and omentum. Although uptake of dexamethasone was decreased in the ischemic myocardium as compared with the non-ischemic myocardium, the ischemic region took up 78% of that taken up by normal myocardium. Pancreatic tissue accumulated significantly greater quantities of <sup>3</sup>H-dexamethasone in cats subjected to myocardial ischemia than in sham-operated controls. <sup>3</sup>H-dexamethasone did not undergo significant metabolism by the heart in the first 2 h following coronary occlusion or after an equivalent sham operation. These data are consistent with a rapid uptake mechanism of glucocorticoid by myocardial tissue. The data also indicate that the large amounts of exogenously administered glucocorticoid remain essentially intact in the heart during the first 2 h of the ischemic process.