It has been found that at least two varieties of diphtheria antitoxin are formed in subjects who are hyperimmunized with diphtheria toxoid (1, 2). In a large proportion of individuals the immune response is characterized by the simultaneous production of precipitating and non-precipitating antitoxins. A small proportion of subjects form only one or the other of these antitoxins.Because of its close similarity to allergic reagin of the hay-fever variety, skin-sensitizing antitoxin has been selected as a model for further investigations of the qualities peculiar to reagin. The advantages of the diphtheria system over other less well characterized antigen-antibody systems have been enumerated in an earlier publication (1). In view of studies of the egg white system by Vaughan and Kabat (3) which showed that the immediate type of skin reaction is caused by antibodies to trace substances rather than to the major antigenic component, it was important in our studies to demonstrate that skin sensitization is specifically effected by non-precipitating antitoxin. Evidence has been presented (2, 4) which indicates that immediate wheal reactions are caused by non-precipitating skin-sensitizing antitoxin, and that reactions elicited following the intradermal injection of toxoid are due to specific interaction between toxoid and this variety of antitoxin.In order to gain additional information concerning the nature and specificity of immediate wheal reactions, individual protein components of various sera were isolated with the object of analyzing their comparative skin-sensitizing abilities. It has been demonstrated (5) that the highly purified gamma globulin fraction obtained by cold ethanol precipitation (6) from a serum conraining non-precipitating, skin-sensitizing antitoxin has lost most of its ability to cause immediate wheal reaction although a corresponding antitoxin loss does not occur.