Seventy-six endomyocardial biopsies obtained from 60 patients receiving adriamycin (ADM) and other anthracycline analogs were studied. The biopsies were studied by light and electron microscopy. Two main types of myocyte degeneration were consistently present, the lesions were focal, and inflammatory infiltrate was absent. The severity of pathologic changes was graded on a scale from 0 (normal) to 3 (marked abnormality). Twelve patients receiving previous mediastinal irradiation (600-5700 rads) showed a mean pathology grade (2.0 +/- 0.89) that was significantly higher than in those patients receiving a comparable dose of ADM but who were not irradiated (1.18 +/- 0.23) (P less than 0.01). This study indicated that radiation, even if remote, enhances ADM-induced cardiotoxicity and evokes a "recall" phenomenon of latent acute irradiation changes. Our data suggest that a specific, progressive, subclinical injury to the heart occurs with anthracycline therapy that cannot be detected reliably by conventional tests. Anthracycline-induced cardiotoxicity in rabbits, monkeys, and dogs shows the same basic cellular lesions as in man. The analogs, adria-DNA and rubidazone, also show lesions similar to those produced by ADM in the human heart. The endomyocardial biopsy is a reliable method for monitoring cardiac damage due to anthracyclines in man.