It has been proposed that administration of pharmacologic doses of glucocorticoids may be beneficial in the setting of acute myocardial ischemia because of their ability to stabilize lysosomal membranes and thereby to prevent the leakage of proteolytic enzymes into the cytoplasm and interstitium. We collected cardiac lymph in anesthetized open-chest dogs in successive 2-h periods and used acid phosphatase as our marker lysosomal enzyme. In group 1 (n=5), we studied the effect of time alone. In these dogs, the total amount of acid phosphatase decreased (P less than 0.05). In group 2 (n=5), methylprednisolone, 30 mg/kg iv, was given. This drug did not change any variable we measured. Ligation of the circumflex coronary artery in group 3 (n=7), produced a significant increase (P less than 0.05) in the amount of acid phosphatase drained from the heart compared to group 1. In the dogs of group 4 (n=5), methylprednisolone did not reduce, and may have augmented, the total amount of acid phosphatase draining from the heart. Thus glucocorticoids do not appear to reduce the amount of acid phosphatase released by the ischemic myocardium into the cardiac lymph.