The anterior chamber of the eye is an immunologically privileged site. Recent evidence indicates that this privilege is an actively acquired immune state in which a unique form of systemic immune deviation exists, anterior chamber-associated immune deviation (ACAID). ACAID is characterized in part by the generation of Ag-specific splenic T lymphocytes that mediate suppression of induction and expression of delayed hypersensitivity and that suppress production of C-fixing antibodies. Delayed hypersensitivity and C fixation are usually associated with extensive nonspecific inflammation and innocent bystander tissue injury. It is, therefore, believed that ACAID represents physiologic adaptations of the immune system that mitigate wanton destruction of the anatomically delicate visual axis, thereby preserving sight, while at the same time providing selective immune protection. As a means of examining the potential contribution of the eye to ACAID induction, we have studied the immune properties of blood harvested from mice that had received BSA into the anterior chamber 48 h earlier. We found that an Ag-specific "signal" is present in the blood of these mice; when blood was transfused into naive syngeneic mice, regulatory cell populations were induced and the recipients were unable to display BSA-specific delayed hypersensitivity. Further analysis of this signal revealed it to be associated with the leukocyte fraction, but not with either the plasma or RBC components of whole blood. Among leukocytes, the suppression-inducing activity correlated positively with cells bearing the mature macrophage marker F4/80 and negatively with cells bearing Thy-1, surface Ig, and class II MHC molecules. These findings are discussed with regard to the potential intraocular sources of the ACAID-inducing signal and the possible mode of action of this factor.