The explant culture of small skin specimens is a good model of in vivo epidermal growth. In this model epidermal cells are not dislodged and remain in vitro under the influences of the original mesenchyme, at least during early growth. Recently we attempted to grow epidermal cells from the skin lesions of some acantholytic dermatoses (Darier's disease [DD], Hailey-Hailey's disease [HHD], and pemphigus vulgaris [PV]) in explant culture, and we observed the behavior of outgrown epidermal cells for a relatively short time after explantation. The cell outgrowth from the skin of a patient with PV, which seemed to be apparently normal but showed positive Nikolsky's sign, formed a well organized flat sheet 48 to 96 hours after explantation, as seen in cultures of normal human adult skin. In contrast, the outgrown cells from the skin lesions of three patients with DD, as well as those from three patients with HHD, showed a characteristic disorganized outgrowth. They did not form the well-organized flat sheet, but showed a marked cell dissociation and conspicuously increased locomotive ability. These findings seems to clearly exhibit the processes of "acantholysis" in vitro and strongly suggest that the cells from these 2 latter dermatoses have a genetically determined insufficiency or defect in cell adhesion. From these results the authors conclude that the mechanism of cell dissociation in DD and HHD is fundamentally different from that in PV.