This report provides a quantitative analysis of the distribution of helper-inducer T cells (H-I, LEU3A +) and cytotoxic-suppressor T cells (C-S, 0KT8 +) performed in a standardized fashion on material from 10 cases of multiple sclerosis. Particular attention was paid to cells at the plaque edge and to normal appearing white matter adjacent to plaques. Numbers of both the C-S and the H-I subset peaked directly at the edges of plaques, whether histopathologically active or inactive (P < 0.01). Normal appearing areas outside active plaques had fewer C-S cells than equivalent areas outside inactive plaques (P < 0.05). A study of three whole plaques showed that the sum of the two T cell subsets was significantly greater than the number of cells bearing the pan-T cell marker in two plaques and in two border regions. The present results support a crucial role for the balance of T cell subsets in the evolution of plaque margins. When taken together with similar findings in experimental allergic encephalomyehtis, they suggest that helper-inducer cell dominance at the border is nesessary for plaque expansion while C-S dominance in non plaque areas is associated with controlled disease. In addition, they suggest either modulation of the OKT3 surface antigen or the presence of a non-T cell bearing OKT8 in association with the site of histopathological change.