The eye has been considered for a long time as a privileged site, where the normal immune response is not manifested. Using a model of orthotopic corneal allografts in mice we demonstrate that both transplantation immunity and tolerance are expressed in the eye. In two strain combinations, one having genetic disparities at the major histocompatibility complex (MHC) and non-MHC antigens and the other with antigenic differences only in non-MHC antigens, survival of corneal allografts was evaluated in normal unmodified recipients, in recipients presensitized with a skin allograft, and in mice made specifically tolerant to the donor alloantigens. While the corneal allografts in unmodified recipients underwent rejection leading to graft failure in 40-50% of the recipients, all corneal allografts in presensitized recipients were rejected. On the contrary, corneal allografts performed in neonatally tolerant recipients enjoyed survival comparable to that of syngeneic grafts. No significant differences in corneal allograft survival were found between MHC antigen compatible and MHC antigen incompatible strain combinations. The results demonstrate that transplantation immunity and tolerance are efficiently expressed in the eye. Consequently, the local regulatory mechanisms must be responsible for the characteristics of immunity after intraocular immunization and for a high degree of acceptance of corneal allografts in normal recipients.