The forkhead family transcription factor FOXP3 has been shown to be critical for the development and function of CD4+ CD25+ regulatory T cells. Recently, FOXP3 expression has been shown to be induced upon activation of human CD4+ T cells. A new report in this issue of the European Journal of Immunology shows that expression of FOXP3 in activated T cell leads to hyporesponsiveness, but not necessarily to acquisition of suppressor function. This finding suggests a new role for FOXP3 in human CD4+ T cells: down-modulating responses to TCR-mediated stimulation.