Effects of a range (2-50 Gy) of single doses of 250 kV X rays on epidermal Langerhans cells in vivo were quantified in groups of CBA/CaH mice. Animals were sacrificed and compared with controls on the 10th day after local irradiation of their hind feet, when Langerhans cell numbers were at a minimum. ATPase-positive Langerhans cells in sheets of footpad epidermis were counted by light microscopy and cells with Birbeck granules were enumerated by electron microscopy. Both methods revealed a dose-dependent loss of Langerhans cells after ionizing radiation. Fifty percent of the ATPase-positive cells were lost after 14.4 +/- 1.3 Gy, and 50% of Birbeck granule-containing cells were lost after 17.9 +/- 4.2 Gy, suggesting that differentiated epidermal Langerhans cells are radioresistant. Loss of equivalent proportions of ATPase-positive and ultrastructurally identifiable cells after a range of doses indicates that X rays do not merely alter Langerhans cell surface markers but actually deplete the epidermal population of these cells.