The lesions of atherosclerosis are responsible for changes in the heart that can lead to myocardial infarction, in the brain to cerebral infarction or stroke, and in the peripheral vasculature to gangrene and loss of function. Lesions of atherosclerosis represent the principal cause of death in the United States, Europe, and part of Asia (58). The advanced lesions of atherosclerosis, the sources of these potentially disastrous clinical events, consist of an extensive inflammatory, fibroproliferative response that intrudes into the lumen of the affected artery, compromises the flow of blood and, thus, oxygen to the affected part, and leads to clinical sequelae. The lesions represent a culmination of interactions between two types of leukocytes, circulating blood monocytes and T lymphocytes, that interact with the lining endothelium, enter into the artery wall, and have the potential to release various bioactive molecules. Ultimately, these interactions result in the migration and proliferation of smooth muscle cells, which elaborate connective tissue within the intima of the affected artery and produce the advanced lesions of atherosclerosis. Platelet mural thrombi and, later, occlusive thrombi can markedly affect the progress of the disease and lead to sudden death. Thus three cellular components in the circulation-monocytes, T lymphocytes, and platelets-together with two cells of the artery wall-endothelium and smooth muscle-interact in multiple ways to generate the lesions of atherosclerosis. The nature of the cells, their inter actions. and the molecules they form represent the subject of this review.