Endomyocardial biopsies were examined in 12 patients receiving total doses of Adriamycin from 90 to 445 mg/M2. These patients had also received previous mediastinal irradiation (from less than 600 to 5700 rad) over periods varying from 6 months to 14 years prior to the endomyocardial biopsy. Severity of pathological change in these 12 patients was compared with that of dose-matched control patients who had not received mediastinal radiation. The severity of the histopathologic changes was scored on a scale from 0 (normal) to 3 (marked abnormality). The mean score of the group receiving irradiation (2.0 +/- 0.89) was significantly higher than the score in those not irradiated (1.18 +/- 0.23) (p less than 0.001). Morphological demonstration of a "recall phenomenon" of latent radiation changes by Adriamycin was demonstrated in small intramyocardial vessels. This study indicates that radiation, even if remote, enhances Adriamycin-induced cardiomyopathy. Therefore, Adriamycin must be given cautiously in patients who have received previous mediastinal radiotherapy.