Previous reports from this laboratory have pointed out the importance of agar precipitin technics as tools for the analysis of human streptococcal infections, as well as of infectious diseases generally (1-6). The use of human convalescent serum as antibody source enabled the estimation of the number of toxins or antigens released by the microorganism in the tissues during the course of the illness. The same system also enabled us to follow the purification of each of the antigens thus shown to be produced in rico. Our studies have revealed that a very large number of streptococcal extracellular antigens were demonstrable with human sera or gamma globulin, but very few cellular products appeared to reach antibody-forming sites in significant amounts. For this reason, much of the recent effort in this laboratory has been devoted to the purification of the extracellular streptococcal components. Thus far, approximately nine of the twenty antigens detected with human gamma globulin have been purified to a greater or lesser degree.The ultimate goal of these studies was to examine the pathogenetic and biological significance of each isolated antigen and to determine its identity and properties. The present report records the first attempt to assess the pathological significance of some of these components. Particular stress has been placed on streptolysin O because of its possible significance in the pathogenesis of rheumatic fever. Several of the other separated antigens have also been tested for their systemic effects.Rheumatic fever is well known to be preceded by streptococcal infections, and strong evidence indicates that this microorganism causes the disease (7). The precise mechanism has never been established, however. It has been suggested that rheumatic fever may be the result of an unusual intoxication by some product or products of the streptococcus (8), or that hypersensitive (9), or autoimmune mechanisms (10) are operative. Whatever the mechanism, the specific cause and effect relationship between streptococcal infection and rheu-* These investigations were assisted by research grants from the Office