This investigation was prompted by our ignorance of the way in which salicyclic acid aids desquamation. Salicyclic acid in aqueous cream or white soft paraffin and in concentrations of 2-12% was applied to normal skin of twenty-three subjects while the vehicle alone was applied to the contralateral sites. Biopsies and skin surface biopsies were taken from the test and control sites after 1 week. Histological examination showed that there was less horny layer on the test specimens but that there were no qualitative or quantitative differences in the structure of the viable epidermis. Portions of the biopsies were incubated in the presence of tritiated precursor compounds and subsequent autoradiographic examination showed no difference in the incorporation of thymidine, cytidine or histidine between test and control preparations. Scanning electron microscopy of skin surface biopsies showed some changes in all specimens--presumably due to hydration--but also showed striking differences between test and control sites and were especially marked with higher concentrations of salicylic acid. It is suggested that salicylic acid causes desquamation by dissolution of intercellular cement material.