Immunohistochemical staining of 16 brains post mortem from patients with progressive multiple sclerosis and of two biopsy specimens from patients with acute demyelinating disease was performed using a panel of monoclonal antibodies reactive with T cells and T-cell subsets, B cells, and Ia (HLA-DR) antigens. Lymphocytic perivascular cuffs were most prominent at the edge of active plaques and were occasionally seen in areas with no evidence of demyelination or macrophage infiltration. Perivascular cuffs consisted predominantly of T cells and Ia+ cells, with many T8+ cells and variable numbers of T4+ cells. T8/T4 ratios in cuffs varied between 1:1 and 50:1. In normal-appearing white matter, cuffs were sparse and were predominantly T8+. The distribution of T cells in the parenchyma resembled that seen in perivascular cuffs, namely, predominantly T8+ cells and variable numbers of T4+ cells. Many Ia+ cells were present in active lesions, and the majority of these cells appeared, by histological criteria, to be macrophages. Tissue macrophages were also stained lightly by the anti-T4 antibody. No brain had more T4+ than T8+ cells, determined using both T4 and Leu3a monoclonal antibodies. B1+ cells were rare. These results suggest that the cellular infiltrate in multiple sclerosis consists predominantly of T cells and macrophages and that there is an overrepresentation of T8+ cells compared with T4+ cells.