DNA repair in human epidermal cells, a target of skin carcinogenesis, was examined by measuring unscheduled DNA synthesis on autoradiographs. Epidermal cells were obtained from normal subjects and all experiments were performed on primary cultures. UV-irradiation induced unscheduled DNA synthesis in human epidermal cells dose-dependently at doses of 5 to 20 J/m2. The range of induction varied 3-fold in 9 cultures derived from different donors. No correlation was found between the extent of unscheduled DNA synthesis and the age or sex of the donors. For comparison, human dermal fibroblasts and mouse epidermal and dermal cells were examined under the same conditions. In human dermal cells, the number of grains was about 3.3 times that in epidermal cells. Mouse epidermal cells isolated from newborn C3H/He and Sencar mice showed almost the same extent of unscheduled DNA synthesis as human cells, but the response of dermal fibroblasts of mice was about 2 to 3 times less than that of human fibroblasts. The relevance of these differences among individuals, cell types and species is discussed.