The aim of this study was to test the efficacy of captopril, an angiotensin-converting enzyme inhibitor and a known suppressor of fibrosis, in preventing late radiation-induced cardiac pathology. Myocardial functional, histochemical and ultrastructural-morphometric studies were done on perfused hearts of rats isolated 3 and 6 months after 60Co γ irradiation with 20 Gy and age-matched controls. At each time the animals were divided into the following groups: nonirradiated controls; irradiated once with 20 Gy; irradiated as above and given daily doses of captopril; daily doses of captopril without irradiation. The results showed that captopril, while ameliorating the decrease in the indices of capillary function, increase in mast cells, fibrosis, number of atrial granules, and changes in nerve terminals, failed to prevent the progressive functional deterioration of the hearts after irradiation. These findings suggest that an intramyofiber derangement may be involved in the long-term myocardial complications of irradiation.