Fractionated X-ray irradiation simulating routine radiotherapy (RT) can increase mouse epidermal cell proliferation resulting in a hyperplasic epidermis which is, in some ways, similar to that of human proliferative skin disorders. Dendritic epidermal T cells (DETC), CD4+, and CDS+ cells were studied at various times during daily X-ray irradiation of mouse skin up to 6 weeks. The number of DETC increased during the first week while epidermal cell density decreased but they gradually disappeared during the following weeks when the irradiated epidermis became hyperplastic. CD4+ or CDS+ cells are rare in normal interfollicular epidermis. CD4+ cells are mainly located in the deeper dermis and often around hair follicles in normal skin. Their numbers decreased during the first week, but increased during the third week when hyperplasia developed. The number of CDS+ cells is small in both normal and irradiated skin although they increased in the late stage of continued irradiation. The negative correlation of CD3+ cells and positive correlation of CD4' cells with epidermal cell density support the speculation that one of the functions of CD3+ y6 cells is downregulation of responses mediated by conventional CD4' c y p T cells and suggest that the latter cells play a role in the development of radiationinduced hyperplasia in mouse epidermis.