The antigenic properties of the polypeptide chains of human 7S gamma-globulin have been related to two major non-cross-reacting antigenic determinants of the whole molecule. These determinants, called S and F, were obtained by hydrolysis of gamma-globulin with papain. Antisera against whole gamma-globulin and against S and F fragments were used in techniques of immune diffusion. Light (L) chains of gamma-globulin showed reactions of partial identity with S fragments, and thus are antigenically deficient with respect to these fragments. Antisera directed against F determinants did not react with L chains but did react with heavy (H) polypeptide chain preparations. In addition, the major component of H chain fractions did not appear to contain determinants in common with the S fragments. L chains of a gamma-myeloma protein were shown to be antigenically deficient with respect to the whole myeloma molecule, and antigenically identical with the Bence-Jones protein of the same patient. Correlation of these results with those of previous investigations have led to the conclusions that the S fragment which is known to contain the combining region of antibody molecules, consists in part of L chains or portions of L chains, and that the F fragment, which mediates several other functions of the whole molecule, is composed in part of portions of H chains.