The role of endothelial cells in inflammatory heart disease and rejection after heart transplantation is only partly understood. To determine whether an immune reaction against endothelial cells occurs we examined endomyocardial biopsies from patients with myocarditis (n = 13), dilated cardiomyopathy (n = 23), no clinical rejection (n = 10) and moderate to severe rejection after heart transplantation (n = 10). These were compared to 'normal' donor hearts with monoclonal endothelial-specific antibodies EN4, Pal-E and F VIII-related antigen. Nearly all endothelial cells were stained positively with EN4. There were no significant changes in the binding of the antibodies except in rejection when Pal-E and F VIII-related antigen were significantly increased. It is concluded that apart from their possible role as antigen-presenting cells, endothelial cells are important targets in rejection after heart transplantation. Damage or cytolysis of endothelial cells may cause both altered transendothelial permeability and functional decrease in antigen presentation.