Abstract Ultrastructural localization of pemphigus vulgaris antigen-antibody complexes and their fate during acantholysis were studied in epidermal sheets obtained from the area surrounding the bullae and in acantholytic cells in blister fluid. The distribution of pemphigus vulgaris antibodies already bound to the keratinocytes in early acantholytic lesions was detected with ferritin-conjugated goat antihuman IgG. Ferritin particles were observed on the surface of keratinocytes with particular affinity for desmosomal structures. The acantholytic cells in the blister fluid bound only a small number of ferritin particles on their surface. During incubation at 37° C, pemphigus vulgaris antigen-antibody complexes on the surface of separated desmosomes were internalized and recognized in cytoplasmic vesicles. Endocytosis of separated desmosomes also was observed in vivo when freshly obtained epidermal sheets were immediately processed for routine electron microscopic study. These findings suggest that pemphigus vulgaris antibodies are densely located on desmosomes and that the antigen-antibody complexes, together with other serum proteins on the keratinocyte surface, are internalized by a process of endocytosis.