One hundred and one soft tissue sarcoma patients from an adjuvant chemotherapy study of the Surgery Branch, National Cancer Institute who had received greater than or equal to 430 mg/m2 (range, 430-600 mg/m2) of doxorubicin were followed for evidence of cardiomyopathy. Fourteen patients developed clinical congestive heart failure attributable to doxorubicin. Nine of these fourteen were evaluated by radionuclide angiography (RNA), and all were abnormal with mean ejection fraction both at rest and exercise less than 30%. Sixty-one asymptomatic patients were studied at least once with RNA. In this asymptomatic group, 13 of 61 patients (21%) had abnormal resting left ventricular function. Exercise studies identified an additional 19 abnormal individuals (31%). Overall incidence of cardiomyopathy, as evidenced by RNA, in the asymptomatic group was 52%. By including the fourteen symptomatic patients, the incidence of cardiomyopathy detected either clinically or by RNA in the 75 evaluated patients was 46%. Comparison of patients by age (less than 40 versus greater than 40) revealed a highly significant difference in the incidence of cardiomyopathy (P less than .001). Fourteen of 36 patients (38%) less than or equal to 40 had either clinical or RNA evidence of cardiotoxicity while 32 of 39 (82%) individuals greater than 40 demonstrated cardiomyopathy. No significant difference was seen in those asymptomatic patients in whom RNA was performed less than or equal to 12 months as compared with greater than 12 months after the end of doxorubicin treatment. In the entire group there was no apparent improvement in cardiomyopathy with time, but results suggest that left ventricular function in the group older than 40 years does deteriorate. The cardiac function of patients younger than age 40 appeared to remain stable or possibly improve with time after the completion of treatment. Sex, tumor location, and radiation treatment were not associated with an increased risk of cardiomyopathy. These results emphasize the dangers of full-dose doxorubicin therapy. This high incidence of cardiomyopathy became apparent because of our ability to prospectively evaluate a large group of patients with prolonged life expectancy that received adjuvant doxorubicin chemotherapy after surgery.