SUMMARYTwenty-six IgG-secreting and eight IgM-secreting hybridomas were derived from the synovia of two patients with rheumatoid arthritis (RA), Hybridomas were obtained by fusing a heteromyeloma cell line, SPAZ-4 with synovial mononuclear cells that were not deliberately stimulated in vitro. Over 96% of the IgG-seereting hybridomas produced antibodies which belonged to the IgGl subclass and showed lambda light chain predominance; the latter was not seen in IgM antibodies, where kappa light chains dominated by 3; 1, All IgG antibodies were eationie, Synovial B cells were not exposed to extrinsic stimuli prior to fusion, therefore these results refieet the state of B cell activation and differentiation in vivo. Our results indicate that IgG-secreting B eells in the RA joint are under a selective influence which is, as yet, unidentified. One out of eight IgM-seereting and two out of 26 IgG-secreting hybridomas produeed rheumatoid factors (RF), The IgM-RF specificity for IgG heavy chain subclasses was determined and showed that the monoclonal bound to IgG 1, IgG2 and IgG4 but not IgG3 with exception of IgG3 Goe ofthe G3m (st) allotype, a profile typical of specificity for the Ga epitope. This monoclonal also distinguished a determinant in the Fc region of human IgG which was not present in rabbit IgG, The overall frequency of RF-secreting hybridomas we observed indicates that B cells committed to RF production in the synovium of a seropositive and a seronegative RA patient is below 10%, Keywords human hybridomas synovial tissue rheumatoid arthritis immunoglobulin isotypes