OBJECTIVE There are 2 classes of serum amyloid A (SAA) protein, acute phase (A-SAA) and constitutive (C-SAA). Hepatic synthesis of A-SAA is dramatically upregulated by inflammatory cytokines, while C-SAA is constitutively produced in the absence of inflammation. A-SAA has been shown to attract monocytes, neutrophils, and T lymphocytes, but the function of C-SAA remains to be determined. SAA proteins have been found in both serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA), but have not been characterized with respect to isoform distribution. We determined the relative distribution of A-SAA and C-SAA in serum and SF of patients with RA and compared their abundance to the classic acute phase response protein, C-reactive protein (CRP). METHODS A-SAA (isoforms SAA1, SAA2) and CRP were measured by commercially available ELISA kits. ELISA were developed for C-SAA (SAA4) and apolipoprotein AI (apo AI) in paired serum and SF from 56 patients with RA. RESULTS Concentrations (mean +/- SD) of A-SAA (SAA1,2) in serum and SF are 124 +/- 247, 20 +/- 32 micrograms/ml; CRP 75 +/- 70, 33 +/- 37 micrograms/ml; C-SAA (SAA4) 106 +/-49, 91 +/- 39 micrograms/ml; and apo AI 1.19 +/- 0.32, 0.37 +/- 0.12 mg/ml, respectively. CRP correlated positively with A-SAA in serum or SF and negatively with apo AI in serum. There was no correlation with apo AI in SF. In contrast, there was no correlation between C-SAA and CRP, A-SAA, or apo AI in serum or in SF. Median concentrations of A-SAA in serum and SF (44, 10 micrograms/ml) and CRP (46, 20 micrograms/ml), respectively, markedly differed from the mean values, whereas median concentrations of C-SAA (104, 85 micrograms/ml) and apo AI (1.17, 0.37 mg/ml), respectively, did not. CONCLUSIONS C-SAA concentrations vary in serum and SF independently of A-SAA and CRP levels. The lower concentration of A-SAA relative to C-SAA and CRP in SF suggests that A-SAA could be selectively catabolized in SF or alternatively not well transported into the synovial space.