Immunoglobulin from pemphigus patients binds to the surface of mouse epidermal cells in culture. Cells incubated with pemphigus antibody are easily detached from the culture plates whereas cells incubated with serum from normal patients adhere tightly to the plate. Detachable cells are viable and detachment is blocked by the addition of the proteinase inhibitor alpha 2-macroglobulin and soybean trypsin inhibitor. The anti-cell surface antibody of pemphigus appears to disrupt adhesion between viable epidermal cells by proteinase activation. We will evaluate the morphological events associated with binding of pemphigus antibody to mouse epidermal cells at the light and electron microscopic level, determine if bivalent pemphigus IgG is necessary for biological effect, determine whether lectins can substitute for pemphigus antibody, assess the effect of pemphigus antibody binding on other membrane receptors (e.g., beta-receptor) and cyclic nucleotide levels, evaluate whether pemphigus antibody activates a membrane proteinase or induces secretion of cellular proteinase(s) to the extracellular environment, determine whether proteinase activation depends upon protein synthesis, define the role of microtubules and microfilaments in pemphigus induced epithelial cell detachment, study the effect of appropriate drugs on pemphigus induced cellular detachment and extend the system to human epidermis and other relevant cell systems. These studies provide a unique model which can be used to explore the effect of anti-cell surface antibody upon cell function.