Memory and naïve B cells are considered to play distinct roles in immune regulation. However, the roles of memory and naïve B-cell subsets in multiple sclerosis (MS) have not yet been elucidated. In this study, we examined whether memory and naïve B-cell subsets differ between patients with MS and healthy subjects and whether interferon beta (IFNbeta)-1b can affect these subsets in patients with MS. We also studied these subsets in relapsing and remitting stages of MS. Subjects included 31 patients with relapsing-remitting MS in the remitting stage, of which 15 were treated with IFNbeta-1b and 16 were not treated, and 22 healthy control subjects. For 11 of the 16 untreated patients, blood samples were also obtained in the relapsing stage. Expression of CD5, CD80, CD86, CCR5, CXCR3, CD11a, and CD49d in memory and naïve B cells in blood samples was examined by flow cytometry. The percentages of CD86(+) cells and CCR5(+) cells in the naïve B-cell subset were significantly higher in untreated patients than in control subjects or IFNbeta-treated patients. In patients with MS, the percentages of CD86(+) cells and CCR5(+) cells in the naïve B-cell subset and the percentage of CD5(+) cells in the memory B-cell subset were significantly greater in the remitting stage than in the relapsing stage. These results indicate that memory and naïve B-cell subsets, especially CD86(+) naïve B cells, CCR5(+) naïve B cells, and CD5(+) memory B cells, might be useful in the study of the pathogenesis of and therapy for MS.