The modification of the response of mouse skin to either single or split (24 hrs) graded doses of X rays by topically applied N,N-dimethylformamide (DMF) was investigated. DMF was applied daily for 5 days prior to irradiation. At a radiation dose level producing dry desquamation, DMF enhanced the X ray response by a factor of 1.3. Also, at the same level of response, the fraction of X ray dose repaired in 24 hours was 0.57, whereas for the DMF-treated and irradiated skin, this factor was 0.41, indicating a reduction of about 28% in subeffective damage repair. The times of maximal involvement of the skin reactions were not different in the X ray plus DMF treated mice versus mice receiving x-irradiation only. The data indicate that DMF is able to modify intrinsic radiation sensitivity of mouse skin epithelial cells, possibly through a reduction in the magnitude of the shoulder region of the survival curve.