DNA excision repair was measured in cell cultures derived from human fetal brain, intestine, kidney, liver, and skin following UV irradiation and N-ethyl-N-nitrosourea (ENU) treatment. Cells in early passages were exposed to 5 or 10 J of UV radiation/sq m or to 25 .mu.M-3.5 mM ENU. DNA excision repair was determined by scintillation counting and autoradiography to measure unscheduled DNA synthesis (UDS) and the UV-endonuclease-sensitive site assay to measure pyrimidine dimers directly. The level of UDS following treatment of these cell cultures with UV was both time- and dose-dependent. UDS also increased with increasing doses of ENU up to 350 .mu.M but decreased at doses greater than 500 .mu.M. Cells derived from human fetal brain, kidney, and liver appeared to exhibit lower (50 to 80%) levels of UDS following UV irradiation or ENU treatment than did cells cultured from human fetal skin or intestine. The loss of UV-endonuclease-sensitive sites assayed in skin, liver, and kidney cells over a 24 h period confirmed the differences observed by UDS in these cells. Skin cells removed 50% of the initial pyrimidine dimers from their DNA within an 8 h period and 65-86% in 24 h. Kidney and liver cells, on the other hand, removed only 28 and 32% of the initial dimers, respectively, over a 24 h period. The data suggest differential excision repair responses following UV irradiation and ENU treatment of cells derived from different human fetal organs.