A clinical syndrome of severe cardiomyopathy often accompanies administration of high doses of anthracycline agents. We studied 36 patients serially with radionuclide angiography. At three weeks following drug administration, 8 of 36 patients showed depression of ejection fraction (EF). All had received at least 280 mg/m2 of the drug and 7 had received more than 380 mg/M2. Definite clinical syndromes of congestive cardiomyopathy developed only in patients showing EF depression and in some patients, EF depression developed without signs of congestive heart failure. Ejection fraction studies at 5 minutes, 1 hour, 4 hours, 24 hours, 72 hours, and one week following drug administration showed no changes when compared to immediate preg-drug EF. Seven patients who died during the study underwent histologic examination. Only the single patient with a depressed EF showed histologic evidence of athracycline cardiotoxicity, although all but 1 of these patients had received at least 400 mg/M2. We conclude that serial radionuclide EF just prior to anthracycline administration is a potentially useful predictor of cardiac toxicity, and that EF depression and/or preservation of a normal EF should be weighed in the decision for administering a drug of this type at high dosage levels.