Contact sensitivity (CS) responses to reactive hapten antigens (Ag), such as picryl chloride, are classical examples of T-cell-mediated immune responses in vivo. There is also abundant evidence that T cells exposed in vivo to high intravenous doses of Ag can downregulate CS (high-dose Ag tolerance). To clarify cell types that effect CS and mediate its downregulation, we have studied CS in mice congenitally deficient in alpha/beta T cells (alpha-/- mice). We show that alpha-/- mice cannot mount CS, implicating alpha/beta T cells as critical CS effector cells. However, after high-dose Ag tolerization, these alpha-/- mice can downregulate alpha/beta CS effector cells adoptively transferred to them. The active cells in tolerized alpha-/- mice are gamma/delta TCR+ cells which downregulate CS effector alpha/beta T cells Ag-specifically upon adoptive cell transfer. Moreover, gamma/delta cells can Ag-specifically downregulate IFN-gamma production by CS effector cells in vitro. These findings establish that gamma/delta T cells are not CS effector cells but downregulate CS, in agreement with recent reports that gamma/delta T cells downregulate IgE responses.