The cellular composition of human atherosclerotic plaques has been analyzed in several immunohistochemical studies in recent years. These studies have shown that the main cell types of the plaque are macrophages, smooth muscle cells, and T lymphocytes. To further characterize the T-lymphocyte population in atherosclerotic plaques, human plaque tissue was digested enzymatically and the released cells were labeled with fluorescent antibodies and analyzed by flow cytometry. Fifteen patients undergoing carotid endarterectomy were studied. Sixty-four percent of plaque T cells expressed the low-molecular-weight form (CD45RO) of the leukocyte common antigen (CD45). Many of these cells expressed the integrin very late activation antigen-1 (VLA-1), which suggests that they are in a state of late activation. In contrast, only 1% of peripheral blood T cells from the same patients expressed VLA-1. Other markers of T cell activation, such as Ta1 (CD26) and HLA-DR, were also increased on plaque T cells. The interleukin-2 receptor (CD25), which is transiently expressed after activation, was present on only a small proportion of the cells. Taken together, this analysis of plaque lymphocytes shows that the majority of plaque T cells are memory cells, many of which are in a state of late or chronic activation. This T-cell phenotype may be the result of a preferential recruitment and/or retention of activated peripheral blood T cells or local antigenic stimulation of resting T cells.