Clinical and experimental heart irradiation can cause a variety of sequelae. A single dose of greater than or equal to 15 Gy leads to a reversible exudative pericarditis, occurring in dogs, rabbits or rats at around 100 days. Its time-course is very similar in all species investigated, but there are considerable species and strain differences in severity and incidence. After longer, dose-dependent latency times chronic congestive myocardial failure develops. At histological examination myocardial degeneration and necrosis is observed, which in some species is accompanied by a variable degree of interstitial fibrosis. In rabbits and rats, myocardial degeneration becomes apparent at around 70 days after 20 Gy and is preceded by a marked reduction in capillary density as well as ultrastructural endothelial cell degeneration. Simultaneously to structural capillary damage, a focal loss of the endothelial marker enzyme alkaline phosphatase was observed in rats in areas with subsequent myocardial degeneration. Cell kinetic studies in rabbits and rats revealed a radiation-induced wave of increased endothelial cell proliferation at 30-100 days postirradiation. In the rat it is exclusively seen in conjunction with alteration of endothelial cell marker enzymes. The temporal and spatial pattern of proliferative response exludes endothelial cell death in mitosis as the sole pathogenetic mechanism causing capillary loss and myocardial degeneration. Parallel to development of morphological damage, haemodynamic studies in various rats strains revealed a drop in cardiac output and left ventricular ejection fraction to about 64% of normal values after 20 Gy. In vivo, this slightly reduced cardiac function was then maintained in a steady state for many weeks, probably due to a compensatory up-regulation of cardiac beta-adrenergic receptors. In denervated working heart preparations in vitro, however, these compensatory mechanisms are not effective and stroke volume as well as cardiac contractility show a rapid and steady deterioration. In many respects radiation-induced heart disease conforms to radiobiological concepts of late-responding tissues, showing a chronic progressive time-course and a very pronounced fractionation effect. However, pathogenesis cannot be understood in terms of target cell depletion alone, and experimental evidence indicates the importance of alterations of regulatory mechanisms.