Skin biopsies from 100 patients with untreated lepromatous leprosy from Malaysia, India, Africa, and South America were examined with particular regard to pathological changes in intima, media, or adventitia of blood vessels and to the presence of leprosy bacilli in these layers. Bacilli were found in capillaries, venules, or arterioles in all cases, and in many instances they were present in endothelial lining cells or smooth muscle in large masses (globi). In several cases, solid-staining bacilli in endothelial lining cells were especially prominent. The findings are discussed in relation to a) the continuous bacteremia of lepromatous leprosy, b) the role of endothelial cells in phagocytosis, c) smooth muscle cells of the media as a site in which bacilli may persist, and d) the transmission of human leprosy by biting arthropods.