Effects of 250-kV X rays on epidermal Langerhans cells were studied in CBA/CaH mice. One group received 20 Gy to the feet, another 8 Gy to the whole body, and a third both the 8 Gy whole-body and a 12 Gy local dose to the feet. Mice from each group and controls were sacrificed at intervals from 1 to 64 days later. ATPase-positive cells in sheets of footpad epidermis were counted by light microscopy. The density of Langerhans cells in controls was 1515 +/- 36/mm2 (mean +/- SE; n = 34). By 3 days after irradiation they became rounded and less dendritic and numbers gradually reached a nadir by 10 days, at 18% of controls after 20 Gy and 57% of controls after 8 Gy. Some of the remainder exhibited bizarre morphology and ultrastructural abnormalities. After local irradiation of the feet Langerhans cell numbers recovered rapidly between 14 and 16 days, although their distribution was uneven until 30 days after irradiation. Repopulation was delayed after an 8 Gy whole-body dose by at least 3 weeks. These results demonstrate that high local doses of X rays substantially but transiently deplete the epidermal Langerhans cell population and support the hypothesis that functional hemopoietic tissue is required for extensive Langerhans cell replenishment.