Relapses of multiple sclerosis (MS) are treated commonly with high-dose intravenous methylprednisolone (MP) given over a period of 3-5 days. The mechanisms responsible for the beneficial effects of MP in attacks are not clearly established. It is also controversial whether this treatment may have a long-term effect. Here, peripheral blood samples from relapsing--remitting MS patients in acute relapse were analysed by flow cytometry just before steroid treatment and at different time points after initiation of the therapy. We observed an immediate (day 3) decrease in the percentage of CD4+ lymphocytes, with a relative increase in the memory (CD4+CD45R0+) subpopulation. A longer standing effect of MP on IFN-gamma production, CD54, CCR5, CXCR3 and CD95 (Fas) expression was also observed on CD4+ cells after 1 month of treatment initiation. Six months after the therapy, during clinical remission, no changes due to ivMP therapy were detected. These results support that MP treatment of relapses induces immediate post-treatment and short-term effects on the immune system that could partly account for the clinical and radiological improvement observed in MS patients. However, no conclusion can be drawn as to a possible long-term or even intermediate influence of ivMP treatment on the course of the disease.