F(ab')2 fragments of anti-γE obtained by pepsin digestion and reduced-alkylated anti-γE induced reversed type erythema-wheal reactions in normal individuals and released histamine from leukocytes, whereas Fab′ fragments of the antibody failed to do so. The requirement of two antibody-combining sites in anti-γE for induction of the reversed type allergic reactions suggested that bridging of two cell-bound γE molecules by anti-γE is the initial step of the reactions. On a molar basis, the original antibody and F(ab')2 fragments were comparable in their ability to induce the reversed allergic reactions, but the C′-fixing activity of the fragments was only 0.4% that of the undigested antibody. The results strongly suggested that C′ is not essential for induction of the reversed type reactions.