The distribution of T cells and T cell subsets was examined within the human central nervous system in active lesions from seven patients with chronic multiple sclerosis. The monoclonal antibodies anti-T11, anti-T4, and anti-T8 were used to detect total (whole) T cells, helper T cells, and suppressor-cytotoxic T cells, respectively, and a monoclonal antibody against human Ia was used for macrophages and B cells. Lesion progression was associated with large numbers of T4⁺ cells at the lesion margin and these extended great distances into the adjacent normal-appearing white matter. T8⁺ cells were most commonly concentrated around the lesion margin and displayed a preferential perivascular distribution. Within the lesion center, only a few T cells were found. Ia⁺ macrophages were most numerous within the centers of active lesions and were always present in the adjacent normal white matter. The monoclonal antibodies to T cells did not cross-react with glial cells including oligodendrocytes. These results indicate that T4⁺ cells are actively involved in lesion extension and Ia⁺ cells, in demyelination.