Rheumatoid factor (RF) is the most common autoantibody found in patients with Sjögren's syndrome (SS). To study the genetic origin and the mechanisms acting behind its generation we have characterized and sequenced the immunoglobulin V_H genes used by 10 IgM RF MoAbs derived from peripheral blood of six female patients with pSS. We compared the structure of the RF immunoglobulin V_H genes with those obtained previously from rheumatoid arthritis (RA) patients and healthy immunized donors (HID). V_H1 and V_H4 were each used by four RF clones, one clone was encoded by V_H3 family gene and one by V_H2 family gene. This distribution frequency was different from that observed in RA, where V_H3 was the dominant family, followed by V_H1. Eight different germ-line (GL) genes encoded the clones and all of these genes were seen previously in RA and/or HID RF. Five clones rearranged to J_H6, four rearranged to J_H4 and one to J_H5, in contrast to RF from RA and HID, where J_H4 was most frequently used. D segment use and CDR3 structure were diverse. Interestingly, three out of four V_H4 clones used the GL gene DP-79 that was seen frequently in RA RF. The degree of somatic mutation in the pSS RF was very much lower than seen in RA and HID RF. All the pSS RF clones except three were in or very close to GL configuration. This indicates that there is little role for somatic hypermutation and a germinal centre reaction in the generation of RF from peripheral blood in pSS.