The injection of a variety of antigens, including transplantation antigens, haptens, and viral glycoproteins, into the anterior chamber of eyes of mice produces a characteristic spectrum of immune responses in which suppressed cell mediated immunity dominates. This phenomenon is called Anterior Chamber Associated Immune Deviation (ACAID). Having recently demonstrated that soluble antigens also can induce ACAID in mice, we examined the possibility that an important soluble ocular antigen, retinal S antigen (S Ag) may be capable of inducing ACAID in rats. We have found that injection of S Ag with adjuvant into the anterior chamber of eyes of adult Lewis rats evokes neither a humoral nor a cell mediated immune response that can be detected. However, animals that received S Ag intracamerally in this manner did respond to a subsequent immunogenic dose of S Ag in CFA injected into the hind foot pads, by producing serum anti S Ag antibodies. Importantly, these rats failed to display antigen-specific delayed hypersensitivity. Moreover, lymphoid cells from anterior chamber pre-treated animals, when adoptively transferred, inhibited the development of S Ag-specific delayed hypersensitivity in naive recipients indicating that an active suppression mechanism had been generated. Thus, a soluble antigen injected intracamerally in adult Lewis rats can generate ACAID. The possibility that ACAID may be relevant to the development of S Ag induced uveitis is discussed.