The extent and duration of immunomodulation induced by high-dose corticosteroid treatment of clinical relapse of multiple sclerosis was investigated. Ten patients treated with a 5 day course of intravenous methylprednisolone (IVMP) (500 mg daily) were studied. Circulating lymphocyte subpopulations and mitogen-induced interleukin 2 (IL-2) and γ-interferon (γ-IFN) production were determined immediately before initiation of therapy (day 1), during therapy (24 h after first dose, day 2) and at 24 h and 1 week post therapy (days 6 and 12 respectively). T-cell subpopulation (CD3, CD4, CD8, CD4CD45RA, CD4CD4SRO) levels fell within 24 h of initiation of therapy, rebounded above pretreatment levels at day 6 and normalised I week post therapy. Despite a reduction in total T-cell numbers during treatment, the γδT-cell subpopulation was not significantly altered. HLA-DR expression on B cells and monocytes declined transiently on day 2 to approximately 50% of pretherapy levels. IL-2 and γ-IFN production were reduced during therapy but returned to baseline levels by 24 h post therapy. The effects of IVMP on lymphocyte distribution and function appear to be short-lived and, therefore, may not be responsible for the rapid improvement associated with this form of treatment.