In a study of ectopically transplanted rat hearts, all grafts showed minimal acute epicarditis and transient electrocardiographic patterns of injury for 24 to 48 hours. Isografts showed no further acute histopathologic changes and had relatively normal electrocardiograms for as long as 290 days. First-set homografts had subendocardial and perivascular mononuclear-cell infiltration three days after transplantation. By the fifth day, generalized mononuclear cell infiltration of the myocardium, interstitial edema, and vascular endothelial edema were evident; electrocardiograms at this time were similar to those of the isografts. Within 7 to 8 days, homografts showed extensive myocardial necrosis although cellular infiltration had lessened. Vascular edema was more prominent but fibrinoid necrosis was not observed. Electrocardiograms, which differed from those of the isografts, showed flattened T waves and defective intraventricular conduction. Electrical activity was lost 9 to 13 days after transplantation. Grafts placed in sensitized hosts had extensive mononuclear-cell infiltration of the subendocardium and myocardium, interstitial edema, and vascular endothelial edema three days after transplantation. Electrocardiograms showed flattened T waves and defective intraventricular conduction 4 to 6 days after transplantation, and electrical activity was lost within 5 to 10 days. For 2 to 5 days preceding loss of electrical activity, therefore, homografts had a specific electrocardiographic pattern which could be used as a precise criterion of rejection.