The clinical course of late symptomatic anthracycline cardiomyopathy, and resultant changes of cardiac function, were described in 15 patients. They represented a subset of 300 patients who had cardiac evaluations to identify the prevalence of late cardiotoxicity more than 4 years after anthracycline therapy in these patients. The clinical course and all available cardiac evaluations including electrocardiography, continuous taped electrocardiography, echocardiography, radionuclide cardiac angiography, cardiac catheterization, and endomyocardial biopsy, of the 15 patients were reviewed. The patients had received 285-870 (median 540) mg/M2 of daunorubicin and/or doxorubicin 6-19 (median 12) years prior to the onset of late symptoms. Seven patients also had 2,100-4,000 cGy mediastinal radiotherapy. Five patients had required treatment for cardiac symptoms at the end of chemotherapy but 10 patients had no cardiac problems anteceding their late decompensation. Fractional shortening on echocardiogram at late decompensation was 8-20% (median 17%) and radionuclide left ventricular ejection fraction was 8-59% (median 38%). All were treated with digitalis and diuretics and 13/15 with afterload reduction, with at least transient improvement of symptoms. They were followed for 1-9 (median 3) years after late decompensation. One died of uncontrollable cardiac failure. Another underwent successful cardiac transplantation. Conduction abnormalities and dysrhythmias were present in 14/15 patients and 3 died suddenly. Two more had syncope, one requiring an automatic cardiac defibrillator. Endomyocardial biopsy or autopsy revealed hypertrophy and fibrosis in 10/10 patients. Our patients with early cardiac symptoms improved transiently but decompensated later and patients with no early symptoms developed cardiac symptoms more than 10 years after anthracycline therapy. Therefore, patients who have received anthracyclines should have continued cardiac evaluation.