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Summary Although the rheumatoid factors (RF) are believed to be relatively insoluble in dilute salt solutions, considerable RF activity in pseudoglobulin fractions was encountered on examination of certain sera of persons having rheumatoid arthritis. Evidence was furnished that pseudoglobulin RF, rather than being laboratory artifacts, represent discrete molecular species. Pseudoglobulin RF were isolated from a number of sera and shown to resemble euglobulin RF with respect to their belonging to the γ1M-immunoglobulin class and with respect to a number of physicochemical parameters, including behavior on ion-exchange chromatography and sedimentation coefficient. Two of the sera examined contained unusual RF, which sedimented considerably more slowly than the usual 19 S globulins, lacking also the antigenic characteristics of γ1M-globulins. One of the serum samples contained one or two RF which were neither related to γ1M- or γ2-globulins, withstanding reduction by mercaptoethanol without loss of biologic activity. On direct comparison of pseudoglobulin RF and euglobulin RF of the γ1M-globulin type from the serum of a person with Waldenstrom's macroglobulinemia, no difference could be detected in their immunologic and serologic behavior. The euglobulin RF, however, appeared to differ some-what from its pseudoglobulin counterpart with respect to sedimentation coefficient, aggregative behavior and amino acid content.