Pulmonary vessels from 26 patients with pulmonary veno-occlusive disease were studied histologically and morphometrically. In addition to the well-known obstruction of veins and venules, pulmonary arteries were also narrowed or obliterated in approximately half of the patients. It is unlikely that the arterial intimal fibrosis, which was sometimes as severe as the fibrosis in the veins, was secondary to the venous obstruction; rather, like the venous alterations, it probably resulted from organization of thrombi. It is possible that primary damage to the vascular wall elicited thrombosis. Such an injury may also have caused the arterialization of the venous walls, a common finding that cannot always be explained by distal narrowing of larger veins. Although the etiology of pulmonary veno-occlusive disease is obscure, it seems increasingly likely that multiple noxious agents may induce this condition. In children no predilection for either sex has been observed, but in adults, men are affected twice as often as women.