Homoreactant (HR), a new naturally occurring serum factor, was shown to react specifically with fragments (Fab) of homologous gamma G-globulin produced by digestions with papain. The reaction was demonstrated by agglutination and agglutination-inhibition experiments utilizing human O Rh (+) erythrocytes sensitized with the Fab fragments of rabbit antibody to human O Rh (+) erythrocytes. Unsensitized cells or cells sensitized with the intact antibody were not agglutinated by HR. Gel-filtration experiments were also used to demonstrate the reaction of HR with the Fab fragments. Pepsin digestion did not affect HR activity; it was destroyed, however, by papain digestion. HR is probably a 7 S, naturally occurring, bivalent antibody which reacts with antigenic determinants buried in the intact gamma G-globulin molecule and exposed after papain digestion.