Human immunodeficiency virus (HIV) infection has impacted on all the systems of the body, and the cardiovascular system is no exception, with small to medium-sized vessel vasculitis being most frequently described. We present 16 HIV-positive patients with large vessel disease consisting of either aneurysms (often multiple) or occlusive disease. Nine men and 7 women ranging in age from 18 to 38 years presented with rupture of aneurysm, transient ischemic attacks, hypertension, ischemia to the lower extremity, or a mass at the site of the aneurysm. Eight patients had 1 aneurysm, 2 had 2 lesions, and the remaining 6 cases had from 3 to 7 aneurysms. Arteries affected included the common carotid, abdominal aorta, common iliac, femoral, and popliteal. Three patients had intercurrent infections, but none had any obvious infective vascular lesion. Only 1 patient had a positive TPHA test for syphilis. Microbiologic culture of both blood and thrombus contents was positive for Staphylococcus aureus in 1 case; no other organisms were cultured. The key histological features were within the adventitia: leukocytoclastic vasculitis of the vasa vasora and periadventitial vessels, proliferation of slit-like vascular channels, chronic inflammation, and fibrosis. There was associated medial fibrosis with loss and fragmentation of muscle and elastic tissue. Intimal changes consisted of duplication and fragmentation of the internal elastic lamina with calcification. Atheroma and marked intimal thickening were not evident We believe that the occurrence of this large vessel vasculopathy (mainly aneurysmal) often with multiple lesions in young HIV-positive patients, is characteristic of possible infective or immune complex origin, with leukocytoclastic vasculitis of vasa vasora and periadventitial vessels being pivotal in many cases.