Embryonic DA retinal allografts that have survived for prolonged periods after having been transplanted into the brains of neonatal BN rats can be induced to reject following peripheral sensitization with a DA skin graft. The results show that histocompatibility antigens play the major role in the rejection of grafts placed in the CNS and that a disparity between the retinal and skin grafts for MHC antigens induces a more severe rejection response than does a non-MHC antigen disparity.