The pathogenic effect of the intercellular antibodies of pemphigus was studied by using organ culture of monkey skin. Skin explants that were grown on sera with intercellular antibody titers of 320 or greater fixed these antibodies within one day as demonstrated by direct immunofluorescence for IgG. None of the control sera gave such staining patterns. Following the binding of intercellular antibodies, characteristic histologic changes appeared, notably separation of individual epidermal cells and acantholysis. These histologic changes became more marked in two to five days. During this period, the bound antibodies and the intercellular antigens decreased and disappeared. These temporal relationships of immunofluorescence and histologic findings suggest that pemphigus antibodies play a role in the induction of acantholysis.