Low-molecular-mass copper(lI) species have been detected and quantified in ultrafiltrates (n = 7) of rheumatoid synovial fluid (SF) by a highly-sensitive HPLC-based assay system with the ability to determine Cu(II) concentrations of < 10 -7 mol.dm -3. High field 1H NMR spectroscopy demonstrated that addition of Cu(II)¢,q.) to isolated samples of RA SF ultrafiltrates resulted in complexation by histidine > alanine > formate > threouine > lactate • tyrosine • phenylalauine, their effectiveness in this context being in the given order. CD spectra of Cu(H)-treated samples of intact SF exhibited absorption bands typical of copper(II)-albumin complexes, in addition to a band attributable to a low-molecular-mass histidinate complex (A~ 610 nm). Since both albumin and histidine are potent radical scavengers, these results indicate that any "OH radical generated from bound copper ions will be 'site-specifically' scavenged. ttence, low-molecular-mass copper complexes with the ability to promote the generation of "OH radical which can then escape trom the metal ion co-ordination sphere (and in turn, cause damage to critical biomolecules) appear to be absent from inflammatory SF.