The expression of connexin 43 (Cx43) in normal and irradiated mouse skin was evaluated using immunofluorescence with polyclonal antisera to Cx43 on cryostat sections. One week after the start of daily irradiation with 3 Gy, enhanced immunoreactivity in basal cells and in the lower part of the spinous layer of the epidermis was detected. In hypertrophic and hyperplastic skin, about 3 weeks after irradiation, a further increase in the expression of Cx43 was found in the epidermis as well as in the dermis. Western blot analysis of normal and irradiated skin homogenates confirmed the increased Cx43 protein concentration in the skin. In nuclear extracts of the same preparations, increased AP-1-binding activity was found. These data suggest that the gap-junction protein is expressed in response to irradiation of the skin and may be related to the subsequent hyperproliferative response which is associated with accelerated repopulation.