CD6 is a pan-T-cell structure about which very little is known, although certain CD6 monoclonal antibodies have been reported to be mitogenic for T cells. Using a heterogeneous collection of human T-cell clones, we now show that CD6-responders were contained exclusively within the gamma/delta-receptor+ group. Three of seven CD6 antibodies tested stimulated autocrine proliferation of 5 of 7 gamma/delta but 0 of 13 alpha/beta T-cell clones. Stimulation was dependent on the presence of accessory cells, which could not be substituted by interleukin 1 beta or 6. These results suggest that a subset of human T cells carrying gamma/delta antigen receptors may be selectively stimulated by the as yet unknown CD6 ligand.