A large body of information exists describing the inability of animals receiving inoculations of antigen either intravenously (i.v.) or via the anterior chamber of the eye (AC) to mount delayed hypersensitivity (DH) responses to the injected antigen. Evidence indicates that the deviant humoral and cellular immunity that follows AC and i.v. inoculations of antigen is mediated, in part, by active suppression. Because of these similarities, it has been argued that immune deviation resulting from the AC inoculation [anterior chamber-associated immune deviation (ACAID)] of antigen represents nothing more than deviant immune responses known to be induced by the i.v. inoculation of antigens. Since circumstantial evidence suggests that AC injections may have unique immune effects, we wished to test the hypothesis that AC exposure to antigen elicits a unique form of systemic immune regulation. We have studied and compared the functional and phenotypic properties of suppressor cell populations induced by AC and i.v. inoculations of a soluble antigen, bovine serum albumin (BSA). Results indicate that AC inoculations of BSA (but not i.v. inoculations) activate antigen-specific. CD8+, I-J+ T lymphocytes which suppress the expression of DH responses, i.e. efferent suppression. We further report that AC and i.v. injection routes both activate antigen-specific afferent suppressor cell populations which impair the inductive phase of the immune response. However, the i.v.-induced afferent suppressor cells are CD8+ I-J+, whereas the AC-induced afferent suppressor cells are CD4+. We conclude that AC and i.v. exposures to soluble antigens are not immunologically equivalent, and that ACAID represents a uniquely regulated systemic immune response to intraocular antigens.