Antibodies reacting with the cytoplasm of epidermal cells (E.C.A.) were detected by indirect immunofluorescence (I.I.F.) studies of 255 sera in various dermatoses (8/100) and significantly more frequently (46/100) in bone marrow transplanted patients having skin lesions. Bound E.C.A. were only found in 2 cases. E.C.A. were devoid of any diagnostic value and were interpreted as the result of a skin injury liberating skin antigens which stimulated their production. The reaction of E.C.A. in I.I.F. on human skin substrates showed 3 different patterns: in some cases only the basal cell layer was stained; in others only the supra basal layers were stained; in others all the layers were stained. A serum was shown to be able to give the 3 patterns of reaction (or no reaction at all) if different human skins were used as substrate. Autologous skins never gave a basal cell layer staining. These findings support the facts that there are antigenic differences between the basal cell layer and the supra basal layers (with regard to the cytoplasmic antigens); these antigens may be different from 1 subject to the other, supporting the allogeneic nature of this system. E.C.A. are regarded as a useful marker of the human skin cytoplasmic antigens.