Medial attenuation in relation to atherosclerotic plaques is poorly understood. We investigated the potential role of a local inflammatory response. Segments of carotid artery and descending aorta were studied. The samples were grossly normal (n = 10), presented circumscribed atherosclerotic plaques (n = 19) or confluent atherosclerotic lesions (n = 8). Tissues were fixed in formalin or snap frozen in liquid nitrogen. Sections were stained with conventional staining methods and immunohistochemically (smooth muscle cells, macrophages, and T and B lymphocytes). Medial thickness was measured with an ocular micrometer; inflammatory infiltrates and medial vascularization were assessed semiquantitatively. Increasing severity of intimal lesions was accompanied by a significant increase in medial inflammation and vascularization and by a significant decrease in medial thickness. The inflammatory infiltrates in the media consisted of macrophages and T lymphocytes, localized predominantly around vasa vasorum. In advanced atherosclerosis they spread more diffusely. Inflammatory cells of the intimal atheroma also penetrated the media. At sites of inflammation the media contained HLA-DR positive smooth muscle cells with loss of collagen. The media in confluent atherosclerosis was almost devoid of smooth muscle cells, with loss of collagen and focal fibrosis. We postulate that the inflammatory reaction in the media relates to atherosclerosis, has a remodelling effect on medial tissues and may cause medial attenuation.