In order to deduce which cellular molecules react with the sera from patients with rheumatoid arthritis (RA), human and mouse cellular extracts were fractionated stepwise, by ethanol precipitation and their reactivity analysed by Western blotting. It was found that three cytoplasmic molecules with molecular weights of 80,000, 81,000 and 77,000 were immunoreactive and they were identified as ezrin (E), radixin (R), and moesin (M), respectively, by partial amino acid sequencing. Using cDNA clones of these human molecules, recombinant proteins were produced in Escherichia coli and used to enable the antigens to detect the antibodies in the sera of patients with RA. Of 71 sera tested, 24 sera (33.8%) reacted with at least one of three recombinant antigens, although there was no significant correlation between the presence of the antibodies and clinical manifestations, such as disease duration or stage. There was also no discernible relationship to other auto-antibodies such as antinuclear antibodies (ANA) and rheumatoid factor. The results suggest that ERM proteins are possible novel auto-immune target antigens for RA.