Using simultaneous dual direct immunofluorescence the effect of high dose intravenous methylprednisolone on the expression of T lymphocyte differentiation antigens in paired cerebrospinal fluid and peripheral blood samples of nine clinically active patients with multiple sclerosis was studied. Corticosteroid treatment was associated with a clinical improvement in eight out of the nine patients. In cerebrospinal fluid of all patients the treatment was associated with a decrease of CD3+, CD4+ and CD8+ T cells, and of intra-central nervous system IgG synthesis. CD8+ high CD11b+ low suppressor-effector T cells behaved differently in the eight patients who improved with treatment, where they significantly increased, and in the patient without clinical response, where they were almost unchanged. Similar phenotypic changes were found in peripheral blood, and all changes returned towards baseline after treatment. The lower sensitivity to corticosteroids of CD8+ high CD11b+ low T cells could change the balance between immunoregulatory T subsets. In this study the increased availability of a subpopulation mainly composed of T cells with a suppressor-effector function was associated with a clinical response to treatment.