Misonidazole, a hypoxic cell radiation-sensitizer, has been used in vivo to analyze its effect on normal and x-irradiated epidermis. The drug action was evaluated 3 days after being implanted subcutaneously. The response of the epidermis and especially of the basal cells to the drug alone and in combination with x-radiation was studied. The ultramorphological analysis as well as quantitative data on epidermal thickness and keratinocyte volume showed that high doses of misonidazole impair the usual post-irradiation epidermal reaction, thus enhancing the involutional effects of radiation and inhibiting radiation-damage repair, even under conditions or normal oxygenation.