A variety of arterial lesions in both pulmonary and systemic circulations have been described in association with human immunodeficiency virus infection. Such lesions include plexogenic arteriopathy in patients with primary pulmonary hypertension and fibrocalcific arterial lesions described in a variety of organs. Lesions involving the pulmonary veins, however, have not been previously described. We report a case of pulmonary veno-occlusive disease in a 2-year-old child with human immunodeficiency virus infection. In view of the rarity of these vascular disorders, including pulmonary veno-occlusive disease, it seems unlikely for their association with human immunodeficiency virus infection to occur by chance alone. Further work is needed to elucidate the role that human immunodeficiency virus may have in the pathogenesis of such vascular lesions.