The immunophenotypical features of the cellular infiltrates in different types of human atherosclerotic lesions, including diffuse intimal thickening as a potential but controversial precursor lesion, have been examined using monoclonal antibodies. Special emphasis is put on monocytes/macrophages, lymphocytes, and their possible interactions. Immuno-double staining techniques have been employed to study these aspects. T lymphocytes and macrophages were detected in diffuse intimal thickening, fatty streaks, and atheromatous plaques. In some lesions a predominance of suppressor/cytotoxic lymphocytes was found, whereas in other lesions mixtures of T suppressor/cytotoxic cells and T helper/inducer cells were found in ratios varying from 1:1 to 4:1. A substantial number of T cells and macrophages was considered to be immunoactivated because of the expression of HLA-DR and, to a lesser extent, of I12 receptor molecules. The activation was particularly evident at sites of close cell-to-cell contact between monocytes/macrophages and lymphocytes. These observations suggest that a specific in situ immune mediated hypersensitivity reaction is associated with the development of atherosclerosis.