Clinical and serological studies provide evidence for a pathogenetically relevant vasculopathy in acquired immune deficiency syndrome (AIDS); however, the morphological status of the endothelium under conditions of human immunodeficiency virus (HIV)-1 infection is only sparsely documented. In this study we adapted an en face preparation technique of endothelium for use in immunohistochemistry and investigated the aortic endothelium of pre-AIDS and AIDS patients (n = 32) in comparison with an HIV-negative group (n = 17). The control group showed a regular pattern of evenly distributed aortic endothelial cells, whereas the endothelial cell pattern in the HIV-1-infected patients was clearly disturbed. Simultaneously, the degree of leukocyte adherence on the aortic endothelium increased significantly. These changes were accompanied by an up-regulation of the vascular cell adhesion molecule-1 (VCAM-1) and E-selectin (ELAM-1). The endothelium turnover increased, and one-half of the HIV-1-infected patients exhibited HLA-DR (major histocompatibility complex class II) antigen in the aortic endothelium. Our results provide evidence for a profound and repeated injury with regeneration and activation of the endothelium in HIV-1 infection. Injury as well as activation of the endothelium impairs its normal regulatory properties. This could have consequences for the maintenance of the blood-brain barrier; it might influence the immunologically important interaction of the endothelium with T cells; and it might trigger Kaposi's sarcoma.