Summary: Serum fractions from ragweed sensitive patients were heated at 56°C for 2 to 4 hr and the effect of this treatment on the γG-, γA- and γE-antibodies against purified ragweed allergen (antigen E) was studied. After heating, both γG- and γA-antibodies showed radioactive precipitin bands in radioimmunodiffusion, whereas the γE radioactive band was lost. Disappearance of the radioactive γE band on heating is not due to loss of antigen-binding activity of γE-antibody but to loss of precipitability of the protein with anti-γE-antibody. By the heat-treatment, skinsensitizing γE-antibody was changed to blocking antibody. It was also found that a fraction containing γE-globulin nonspecifically blocked passive sensitization of human skin with reaginic antibody, and that the blocking activity of the preparation was lost by heating. The results indicate that the major reason for inactivation of skin sensitizing activity by heating is the loss of affinity of γE-antibody for human skin tissues rather than to destruction of the antibody-combinding sites of the molecule.