A defect of CD4(+) regulatory T cells (Treg) seems to be involved in the pathogenesis of multiple sclerosis (MS). Besides Treg, CD8(+) T cells also can suppress the immune response. Forkhead box p3 (Foxp3) is known to program the acquisition of suppressive capacities in CD4(+) T cells and recent studies showed that in vitro antigen activation leads to Foxp3 expression in CD8(+) T cells, gaining of suppressive activity. By flow cytometry we found a lower percentage of circulating CD8(+)Foxp3(+) T cells in relapsing than in remitting patients with MS and in controls. No significant differences were observed in CD8(+)Foxp3(+) T cell percentage between healthy subjects and patients in remission. Our data suggest that peripheral CD8(+)Foxp3(+) T cells may play a role in the maintenance of tolerance in MS.