Stratum corneum antibodies (SCAb) as detected by indirect immunofluorescence (IIF) can be absorbed from human sera with homogenates of normal human callus which contain stratum corneum antigen. Titers of concomitantly present antibodies remain unchanged in sera absorbed with callus, thus showing that this absorption is specific. SCAb reacting in a passive hemagglutination assay with an antigen derived from human callus by means of a trypsin-phenol-water extraction can be specifically absorbed with the homologous antigen. However, absorption with callus fails to remove the hemagglutinating antibodies and absorption with the trypsin-phenol-water antigen preparation fails to remove SCAb detected by IIF. These data indicate a nonidentity relationship between these antigen systems despite their similar histological and anatomical tissue distribution. Reactivity of immunoglobulins and complement only with areas of traumatized stratum corneum in skin explants cultured on sera containing SCAb provide some insight as to a possible normal physiologic role for these ubiquitous complement-fixing autoantibodies.