The obligate intracellular bacterium Chlamydia pneumoniae has been implicated in the pathogenesis of atherosclerosis since viable pathogen has been recovered from plaques. Chlamydiae are epithelial pathogens notorious for causing persistent infection. Atherosclerosis, however, is a chronic inflammatory disease involving mesenchymal cells of the vascular wall. A bacterial contribution to atherosclerosis appears more relevant if the resident mesenchymal cells of the vascular wall that constitute the plaque can support chlamydial infection continuously. Therefore we inoculated immortalized and primary mesenchymal cells with a vascular and a respiratory Chlamydia pneumoniae isolate. Primary human coronary artery endothelial and smooth muscle cells, primary human embryonic fibroblasts as well as the immortalized cell lines were permissive for continuous growth of both strains. Thus, the resident vascular cells that produce the atheromatous plaque can acquire permanent productive. Chlamydia pneumoniae infection. Immortalized monocytic cells and peripheral blood monocytes also supported chlamydial growth, though productive infection ceased after 5 passages. Monocytes/macrophages are not resident cells of the vascular wall but have an active role in plaque formation. Systemic circulation and transendothelial migration makes them a potential vector system for chlamydial distribution. These findings add further plausibility to the hypothesis of a chronic infectious component in the multifactorial condition of atherosclerosis. Further studies must precisely define chlamydial target cells in vivo and differentiate infection in resident cells of the vascular wall from a presence limited to migrating macrophages. Endovascular infection might provide an explanation for unclear phenomena of atherogenesis like mesenchymal cell proliferation and its distinct inflammatory component.