Interest in the endothelium as a possible initiator or target of the antiallograft response prompted the following study. Immunocytochemical techniques have been used to investigate the expression of the endothelial markers EN4, Pal-E, and FVIII-RA in normal human heart, cardiac biopsies from patients with various cardiac diseases (dilated cardiomyopathy [DCM] and myocarditis [MCO]), and cardiac biopsies from heart-transplant recipients undergoing acute rejection or free of rejection. Quantitative data demonstrated greater preponderance of EN4 cells in normal heart than the other markers. In biopsies showing histologic signs of rejection, there was no difference in the number of EN4 positive cells compared to normal. In contrast, there was found a striking increase in the proportion of cells that are Pal-E positive and a significant increase in the proportion of FVIII-RA positive cells in these biopsies. The patient details provided suggest these results do not reflect vascular damage due to cyclosporine but may well reflect damage caused by the rejection process.