Rheumatoid factors, antibodies directed against the Fc portion of IgG, exhibit considerable isotypic and idiotypic diversity. Differential expression of IgM and IgA rheumatoid factors suggests that isotype-specific regulatory pathways are operative in man. The physical characteristics of IgA rheumatoid factor rheumatoid arthritis have also been investigated. Although the polymeric form of IgA rheumatoid factor generally predominates in sera and synovial fluids of rheumatoid arthritis patients, wide variations in the ratio of monomeric to polymeric IgA rheumatoid factor are observed. Both forms are elaborated by synovial plasma cells. The differences in the proportions of monomeric and polymeric IgA RF present in sera may be of pathogenetic significance is suggested by evidence that complexes of polymeric IgA rheumatoid factor and IgG are potent inducers of lysosomal release by RMN whereas monomeric IgA rheumatoid factor-IgG complexes are essentially inactive in this regard. The idiotypic diversity of rheumatoid factors has also been under intensive investigation. A monoclonal antibody designated 6B6.6 recognizes a Vk-associated idiotype present on approximately one-third of IgMk rheumatoid factor paraproteins, but only a small fraction of polyclonal IgM 6B6.6-defined idiotype is distinct from previously described rheumatoid factor cross-reactive idiotypes. Taken together, these studies underline the extensive diversity of rheumatoid factors present in various conditions. Application of molecular genetic approaches to the study of rheumatoid factors should provide explanations for the molecular basis of this diversity and serve to clarify the relationship among rheumatoid factors expressed in both physiologic and pathologic states.