We have reinvestigated an important issue in the amphibian immunology that has not been settled for years since the pioneer work of Triplett, concerning the necessity of being exposed to organ-specific antigens early in development. It was found that syngeneic lenses were rejected by frogs, Xenopus laevis, that had been enucleated (eye removed) during early larval life. This rejection did not occur in intact frogs or in those enucleated in later larval or adult life. Whereas the splenocytes from intact frogs did not proliferate in response to a co-cultured syngeneic lens, those from frogs that had been enucleated at any of the larval stages, or even after metamorphosis, proliferated intensely. Both of these responses were shown to be thymus- dependent. In conclusion, it was demonstrated that the frog immune system rejected even syngeheic lenses by enucleation in early larval life and that it began to recognize the syngeneic lenses by lymphoid proliferation after enucleation, even in later life.