The binding sites of Concanavalin A (Con A) and pemphigus antibody in the intercellular spaces of the human epidermis have been investigated. Extraction of human skin with phosphate-buffered saline (PBS) and 70% ethanol resulted in complete loss of the binding sites of the pemphigus antibody, whereas the extracted skin still retained its reactivity to Con A. Preincubation with more than 0.25 mg/ml of Con A with normal skin caused a reduction in the binding of pemphigus sera. However, preincubation of pemphigus sera with human skin caused no inhibition of the subsequent binding of fluorescein-labelled Con A. These results indicate that Con A binding sites might be related to, but not identical with those of pemphigus antibody.