Using a murine model of skin allotransplantation, we have demonstrated previously that inhibition of specific response to alloantigen is inducible by immunization of the host with intravenously administered photoinacti-vated antigraft effector T cells. This hyporesponsive-ness, which was demonstrated by specific inhibition of mixed leukocyte culture (MLC), inhibition of cytotoxic T lympholysis (CTL), specific suppression of the delayed type hypersensitivity (DTH) response, and prolongation of specific skin allograft survival, was adoptively transferable by CD8+ radiosensitive T lymphocytes. In this study, we extend those results to evaluate the effects of an immunosuppressive agent (prednisolone) and an alkylating drug (cyclophosphamide) on the induction of this specific suppressive cellular response. Our results reveal that the administration of prednisolone reduces the induction of the specific hyporesponsiveness to alloantigen, as demonstrated by maintenance of the DTH response to alloantigen and continued accelerated rejection of skin allografts. In contrast, the administration of cyclophosphamide augmented this specific suppressive response to alloantigen in the DTH assay and in prolongation of specific skin allograft survival. These results indicate that adjuvant immunomodulating chemotherapy alters the immune response to photoinac-tivated effector T cells.