The capacity of the mammalian brain to support the physiological function of allografts was assessed in parathyroidectomized Fischer strain rats bearing either isografts or immunogenic DA allografts of parathyroid glands implanted in their cerebral cortices. Established isografts and allografts survived indefinitely in the brain, maintaining normal serum calcium levels, with equal numbers of spontaneous failures (18-21%) in each group. Similarly, both MHC-compatible and incompatible skin allografts survived and were 'functional' at 40-50 days postgrafting as assessed by: continued formation of keratin; the presence of differentiated hair follicles and sebaceous glands; and frequent mitotic figures. No serum alloantibodies were induced by either MHC-incompatible parathyroid glands or skin in this site. However, both types of allografts were promptly rejected or failed to become established in the brains of specifically presensitized hosts. Furthermore, when Fischer hosts with long-established intracerebral DA parathyroid grafts received orthotopic DA skin grafts, their parathyroid grafts were rejected along with first-set rejection of the skin grafts. The tempo of this cellular immune response and the primary alloantibody response that accompanied it indicate that although the intracerebral grafts failed to induce detectable host sensitization or suppression, they remained susceptible to immune effectors. Thus, by using strongly immunogenic, adult tissues, we have established that the rat cerebral cortex is an immunologically privileged site, and the privilege is not dependent on lack of graft immunogenicity or alterations in host responsiveness. Furthermore, Ia+ (possible antigen-presenting) cells were rare in the cortical parenchyma sites used for transplantation though numerous in the choroid plexus of the ventricles and in certain areas of white matter. Therefore, privilege probably reflects deficient graft antigen presentation related to the paucity of Ia+ cells as well as to the brain's poor lymphatic drainage.