The anterior chamber is widely recognized as an example of an immune privileged site. It has become clear that the immunologic privilege of the anterior chamber is the result of active down-regulation of systemic cell-mediated immunity, a phenomenon termed anterior chamber-associated immune deviation (ACAID). In murine models ACAID has been demonstrated using tumor antigens, viral antigens, haptenated spleen cells, and minor histocompatibility antigens. In the present study, we examined the role of class II-positive cells of donor origin on the induction of ACAID. DBA/2 splenocytes were sorted into plastic-adherent, class II-positive, and nonadherent, class II-negative. populations and subsequently transplanted into the anterior chamber of allogeneic BALB/c hosts. Hosts primed intracamerally with class II-positive, adherent cells developed strong DTH responses (P less than 0.01) while hosts primed with nonadherent, class II-negative cells failed to mount detectable DTH responsiveness (P greater than 0.05). Similar results were found in a parallel study using the class II-negative CCL 46 and class II-positive AD.4 subclones of the P388D1 tumor line (DBA/2 origin). The class II-positive tumor grew transiently and stimulated a strong DTH response (P less than 0.01), while the class II negative tumor grew progressively and failed to stimulate DTH responsiveness (P greater than 0.05). The results indicate that donor-derived Ia+ antigen-presenting cells can deprive the anterior chamber of its immunologic privilege and lead to the induction of normal systemic alloimmunity.