During the course of investigations aimed at detecting infectious hepatitis virus antigen in human livers from patients dying early in the course of fulminating infectious hepatitis with acute yellow atrophy of the liver, many human sera were found to react with liver antigen with fixation of complement in a manner indistinguishable from classical antigen-antibody complementfixation reactions. It has subsequently been possible to demonstrate specific complement fixation, in some cases in extraordinarily high titer, with human sera from patients suffering from a number of different diseases, using saline suspensions of finely homogenized normal human tissues as antigens. In a preliminary communication1I reported study of 190 human sera by this technique, with the finding of high incidence of positive reactions in disseminated lupus erythematosus, "lupoid hepatitis" (see below), other chronic hepatitides, and macroglobulinemia. The current report is concerned with extension of these studies in these and other diseases and to