OBJECTIVE To determine whether patients with rheumatoid arthritis (RA) from Bermuda and England have an increased anti-Proteus antibody titer when compared to healthy Bermudian and English controls, and to ascertain whether any increase in antibody titer is specific by testing 4 other microbes, Escherichia coli and 3 normal anaerobic bowel bacteria. METHODS Antibody titers were measured by ELISA and indirect immunofluorescence (IIFA) under coded conditions. RESULTS Elevated titers of anti-Proteus antibodies were demonstrated in 34 patients with active RA from Bermuda when compared to 33 healthy Bermudian controls by ELISA (p < 0.001) and IIFA (p < 0.001). An elevation of anti-Proteus antibodies was also observed in 34 patients with RA from England when compared to 30 healthy English controls again by ELISA (p < 0.001). A similar antibody elevation in 31 patients with RA from England was observed when compared to 30 healthy controls when measured by IIFA (p < 0.001). However, there was no significant elevation in antibody titers against E. coli or the 3 normal bowel flora isolates in the patients with RA from both countries compared to their respective controls, when measured by ELISA. CONCLUSIONS A specific elevation in the immune response to Proteus mirabilis has been demonstrated in patients with RA from both Bermuda and England. However, this study cannot distinguish between antibody association with disease per se and association with disease activity. The role of Proteus in RA and the effect of anti-Proteus therapy in patients with RA merits further study.