The question of whether one or more antigens are involved in the reaction between antibodies in human serum and callus of man was investigated. Callus was collected from an individual with congenital hyperkeratosis. Preparations were obtained by extraction of homogenated callus with (1) phenol water (PW), and (2) the combined use of trypsin digestion and phenol water extraction (TPW). The phenol and water phases were studied using indirect haemagglutination technique. All preparations sensitized erythrocytes for agglutination by human serum except for the phenol phase of the PW preparation. Absorption and inhibition experiments showed that one antigen present in the TPW water phase was also present in the PW water phase. In addition, the PW water phase contained another antigen. In the phenol phase of the TPW preparation a third antigen was demonstrated. Serological cross-reactivity between the antigens and bacteria isolated from callus was not demonstrated. The results of immune adherence test with sections of human skin and unabsorbed or absorbed human serum indicated that the two water phase antigens are present in normal human skin.