Cell shedding from plantar stratum corneum was studied in vitro. Cells were shed only from the surface that had faced outwards in vivo. A quantitative measure of the cell release was obtained by determining the amount of protein that could be extracted from released and sedimented cells with 1 M sodium hydroxide. The cell release was optimal at pH 7-9 but was significant also at pH 6. The rate of cell release increased with increasing temperature, but was decreased abruptly at temperatures above 50 degrees C. The cell dissociation could be inhibited by aprotinin (Trasylol) and soybean trypsin inhibitor. Thus, it is evident that the unipolar cell dissociation in this system is mediated by an enzymatically catalyzed process, most likely with the involvement of a serine protease with an alkaline pH-optimum. The in vitro cell release shows properties indicating that it may be mediated by mechanisms also active in vivo.