BACKGROUND The major histocompatibility complexes, MHC class I and II, are found only sparsely or not at all in the retina. Since the eye is immunoprivileged, we decided to investigate how the MHC class I and II antigens were influenced by a retinal transplant and whether this could be correlated to rejection of the transplant. METHODS Fetal neural retinas of Sprague-Dawley (SD) rats were implanted in the subretinal space of adult Lewis and SD rats. After 5 weeks the retinas and the transplants were evaluated with antibodies against MHC class I and II antigens as well as microglia. RESULTS In the syngeneic transplants no upregulation of MHC class I antigen was seen and no MHC class II-positive cells could be detected. In the allogeneic transplants, on the other hand, there was marked upregulation of MHC class I antigen. Numerous MHC class II antigen-positive cells were seen in the subretinal transplant but also in the host retina. CONCLUSIONS Allogeneic retinal transplants seem to grow and thrive just as well as syngeneic transplants, but in the former there is considerable upregulation of MHC expression. Our interpretation of these results is that the allogeneic transplants are recognized as nonself, but that there is also something that modifies this reaction of the immune system at this level, preventing the rejection that would normally ensue.