Purpose. Delivery of antigen to the anterior chamber (AC) of the eye induces a systemic form of tolerance, referred to as anterior chamber-associated immune deviation (ACAID). ACAID is characterized by decreases in delayed-type hypersensitivity responses and complement-fixing antibodies on subsequent challenge with an immunogenic form of the antigen. The current study was designed to test whether priming of antigen-specific CD8+ cytotoxic T-lymphocytes (CTLs) are inhibited by injection of soluble antigen into the AC and whether γδ T cells play a role in the inhibition of such responses. Methods. Antigen was administered through the AC to normal γδ T-cell-deficient or reconstituted γδ T-cell-deficient mice. Seven days after the AC injection, the mice were primed with antigen in adjuvant and 10 days later, their spleen cells were cultured for 5 to 7 days and the CTL responses measured. Results. CTL responses were inhibited by antigen delivered through the AC in normal but not γδ T-cell-deficient mice. Tolerance was reconstituted in δ-chain knockout mice by the adoptive transfer of γδ T cells from normal mice. Moreover, spleen cells and splenic γδ+ T cells, but not γδ- T cells, from mice injected with antigen through the AC inhibited development of CTL responses when cultured together with primed effector T cells. Conclusions. These data show, for the first time, that administration of soluble antigen in the AC inhibits development of CD8+ cytotoxic T-cell responses and that γδ T cells play a critical role in inhibition of CTL responses.