Previous studies have established that exposure of mice to ultraviolet radiation followed by injection of alloantigen can suppress the induction of delayed hypersensitivity and the rejection of allografts in an antigen-specific manner. In the clinical situation, however, UV irradiation several days prior to transplantation may prove impractical due to the difficulty in predicting when a donor organ will be available. Thus, the purpose of this study was to determine if exposure to UV radiation can suppress the elicitation of the immune response in mice sensitized with alloantigen. The data demonstrate that exposure of mice to UV radiation 1, 3, or 5 days after the injection of alloantigen can significantly suppress the delayed hypersensitivity response to that alloantigen. Present in the spleens of these mice are suppressor T lymphocytes. These suppressor cells are specific for the antigen originally used to sensitize the mice, in that they do not suppress the response to an irrelevant alloantigen. In addition, spleen cells from mice sensitized with alloantigen and exposed to UV radiation 1, 3, or 5 days later are unable to proliferate in response to the alloantigen in a mixed lymphocyte response. These cells do respond to irrelevant third-party cells, demonstrating again the specificity of the suppression. These data demonstrate that exposure of mice in vivo to UV radiation can inhibit the elicitation of the immune response to alloantigen. Since the immunosuppression is specific for the sensitizing antigen, these data suggest that this may provide a novel method of suppressing the immune response to tissue allografts.