Postmortem examination of the lungs of a patient with advanced AIDS who had developed pulmonary arterial hypertension late in the course of the illness demonstrated extensive cytomegalovirus (CMV) infection in endothelial cells of the lung microvasculature. Enlarged CMV-infected endothelial cells were present in virtually all histologic sections of the lungs, protruded into and compromised the lumens of the small vessels they lined, and were estimated by image cytometry of immunohistochemically stained sections to comprise 0.8% of the total lung tissue volume. Comparison with experimental microvascular embolization studies suggests that this amount of compromise of the microvascular luminal area of the lung is sufficient to elevate pulmonary arterial pressure significantly. Pathologic features in this case differed from both the plexogenic arteriopathy seen in previously reported cases of AIDS-associated primary pulmonary hypertension and the usual form of CMV pneumonitis in AIDS in which alveolar epithelial cells are the predominant site of infection.