gammadelta T cells may be important innate immune system contributors to the immunopathogenesis of multiple sclerosis (MS), though the mechanisms are not yet fully understood. CD16 is a low affinity Fcgamma receptor, an activation receptor for gammadelta T cells, and a mediator of cytotoxicity. In this study, we found that the percentage of CD16(+) gammadelta T cells is elevated in MS patients compared with healthy controls. The increase is especially pronounced in patients with a progressive course of the disease, and the extent of this elevation shows a positive correlation with the time of disease progression and severity. In vitro cultured gammadelta T cells can be shown to upregulate the expression of CD16 in response to inflammatory cytokines such as IL-2 and -15, that have been shown to be elevated in progressive disease. These results suggest that CD16 expressing gammadelta T cells are somehow involved in the process of disease progression. Understanding more about these cells and their particular function in progressive vs. non-progressive disease could provide important clues to the mechanism of immune-mediated MS disease progression.