Cantharidin has been used to induce acantholysis in vivo. Intraepidermal clefting starts at the junction between the basal and epidermal layers, and later involves all of the levels of the stratum spinosum. As a response to early acantholysis, an increased number of epibasal cells synthesize DNA. This is not related to an increased binding of epidermal growth factor to these cells. In sum, the basal-epibasal junction is one of the weakest within the epidermis. The epibasal cells represent a reserve pool for proliferating keratinocytes that may be stimulated without necessarily binding an increased amount of epidermal growth factor.