Data are presented demonstrating the differential radiosensitivity of the first and second-set responses of sublethally irradiated (670 rad) mice previously sensitized with allogeneic (H-2 difference), xenogeneic (rat), or both allogeneic and xenogeneic skin grafts. The second-set response is more radioresistant than is the first-set response; the secondset response to a xenogeneic graft remains intact during and following recovery from the effects of sublethal irradiation; while intact for a brief period following irradiation, the second-set response to an allogeneic skin graft was abrogated by sublethal irradiation (670 rad); concurrent presensitization with allogeneic and xenogeneic skin grafts did not prevent the abrogation of the second-set response to the allogeneic graft by sublethal irradiation; the first-set response to an allogeneic graft recovered from the effects of sublethal irradiation prior to the recovery of the firstset response to a xenogeneic graft.