OBJECTIVE. Levels of beta 2-microglobulin and modified beta 2-microglobulin (Des-Lys58-beta 2m) were measured in serum and synovial fluids from patients with rheumatoid arthritis (RA) and other inflammatory joint disorders using rabbit antisera prepared against the beta 2m peptide VEHSDLSFS encompassing residues 49-57 and absorbed with the C-terminal beta 2m peptide (87-97) LSQPKIVKWDR. These antisera which did not react with native beta 2m were employed to quantitate Des-Lys58-beta 2m in serum and SF. Native beta 2m was measured using a direct ELISA method. RESULTS. Removal of serum rheumatoid factor by adsorption to monomeric IgG columns did not change serum levels of beta 2m or Des-Lys58-beta 2m. Native beta 2m was found in all of 20 RA sera, but only rarely in SLE sera. No serum beta 2m was found in 20 patients with ankylosing spondylitis or 25 normal controls. Significant elevations of Des-Lys58-beta 2m were found in 80% of 21 SF from RA patients and in 43% of 41 SF from other subjects with various forms of inflammatory arthritis. In RA and other disorders such as gout or pseudogout, levels of Des-Lys58-beta 2m were higher in synovial fluid than in serum during an acute episode of synovitis. Both native beta 2m and Des-Lys58-beta 2m showed minimal neutrophil and T cell chemotactic activity. CONCLUSION. Des-Lys58-beta 2m present in many inflammatory SF may contribute to the inflammatory reaction in many forms of connective tissue disease by its known amplification of T cell cytotoxicity.