We examined radionuclide-determined left ventricular ejection fractions (LVEF) at rest and during graded exercise in 37 patients receiving doxorubicin (Adriamycin) therapy in whom the risk of developing congestive heart failure (CHF) was precisely defined by endomyocardial biopsy and right heart catheterization. Echocardiographic (Echo %FS) and phonocardiographic (PEP/LVET) measurements of LV function were also determined. An abnormal LVEF at rest (less than or equal to 45%) had a sensitivity of 53% and a specificity of 75% for detecting patients at moderate or high risk of developing CHF. The addition of exercise LVEF increased the sensitivity of detection of moderate or high-risk patients to 89% but lowered the specificity to 41%. Exercise LVEF improved the sensitivity of detection of high-risk patients from 58% to 100%. Echo %FS and PEP/LVET yielded lower sensitivities than rest or exercise LVEF. As a single test, exercise LVEF possesses the sensitivity for use as a screening method for anthracycline cardiotoxicity, but the lack of specificity prevents the use of single values as a definitive test. Single rest LVEF determinations, although more specific than exercise LVEF, do not possess the sensitivity for use as screening or definitive tests.