In the serum of most patients with rheumatoid arthritis and some with other collagen diseases, an agglutinating factor is present. The factor is not detectable with a significant incidence in the serum of patients with other chronic arthritides. A variety of agglutinating systems, including sensitized bacteria, erythrocytes, and synthetic polymers, have been utilized to demonstrate the presence of the rheumatoid factor. It is likely, but not certain, that the same factor is concerned in each system. The sensitizing agent is, in all instances, a gamma globulin constituent of variable composition attached to the particulate body, in some cases as an antibody and in others nonspecifically. Agglutination is believed to occur as a result of reaction between the sensitizing factor and the rheumatoid factor. The demonstration of precipitation between fraction II (gamma globulin) and rheumatoid serum supports this point of view. When whole serum is examined electrophoretically, the agglutinating activity is found in the beta and gamma globulin fractions, but when purified fractions are so studied, the activity is usually found in the gamma globulin fraction. It has been suggested that the rheumatoid factor is an autoantibody to gamma globulin. Though it is well established that interaction occurs between this factor and various gamma globulin constituents, it has not yet been proved that the factor is a true antibody. One or more constituents of the gamma globulin fraction of human and rabbit serum have the capacity to inhibit the agglutinating activity of the rheumatoid factor when present in sufficient concentration to bind it preferentially. The presence of an agglutinating factor in the gamma globulin fraction of the serum of patients with rheumatoid arthritis suggests, along with other data, that alterations in the composition of this fraction may play an important part in the pathogenesis of this disease.