This study was designed to investigate the expression of vascular cell adhesion molecule-1 (VCAM-1) and the counter-ligand VLA-4 (CD 49d) in frozen sections of endomyocardial biopsies (EMBs) of heart allografts in relation to the onset of cytomegalovirus (CMV) infection diagnosed by CMV antigenemia. Altogether, 105 EMBs were obtained from 21 heart transplant recipients. Serial EMBs from nine patients with CMV infection, from five patients with rejection, and from seven patients with a noncomplicated postoperative course were analyzed. Associated with CMV infection, capillary expression of VCAM-1 was significantly induced when compared to control biopsies (P < 0.0001). A striking difference in the expression of VCAM-1 during rejection and CMV infection was observed: in most rejecting biopsies only a few capillaries stained faintly for VCAM-1, whereas during CMV infection, multifocal intense staining was found (P < 0.0001).