The eye, brain, and fetoplacental unit within the pregnant uterus are immunologically privileged sites that contain unique fluids with suspected immunoinhibitory properties. Aqueous humor, which is normally present within the anterior chamber (AC) of the eye, has been shown to suppress antigen-driven T cell activation, and to contain significant amounts of transforming growth factor beta-2 (TGF-beta). Antigens injected into the AC of normal mice induce a deviant form of systemic immunity, termed anterior chamber-associated immune deviation (ACAID), which is characterized by a selective inability to display antigen-specific delayed hypersensitivity. It has recently been reported that eye-derived macrophages appear in the blood following AC injection of a soluble antigen, and that these cells can induce antigen-specific ACAID when injected into naive, syngeneic recipients. Moreover, antigen-pulsed peritoneally derived macrophages that are exposed in vitro to aqueous humor, supernatants of cultured iris and ciliary body cells (I/CD), or TGF-beta have been found to assume ACAID-inducing properties. In the present experiments, amniotic fluid and cerebrospinal fluid from mice, rats and humans, as well as supernatants from cultured I/CB cells, have been examined for their capacity to confer ACAID-inducing properties on peritoneal macrophages. It was found that each of these biologic fluids, but neither normal mouse serum nor rat thoracic duct lymph, was able to endow antigen-pulsed peritoneal macrophages with ACAID-inducing properties. Moreover, fluids from these immune privileged sites were found to contain latent and/or active TGF-beta, as determined by bioassay, using neutralizing anti-TGF-beta antibodies. It is concluded (a) that the immune privileged states of the eye, the brain, and the fetoplacental unit share common features, and possess unique fluids with a similar capacity to force macrophages to present antigens in a "deviant" manner and (b) that this capacity is mediated, at least in part, by TGF-beta. These results are discussed in terms of the potential physiologic and pathophysiologic significance of immune privilege in these three specialized tissues.