OBJECTIVE: To investigate the role of citrate in the pathophysiology of arthritides with calcium pyrophosphate dihydrate (CPPD) crystals and/or apatite-like material. METHODS: We measured citrate concentrations in the plasma and synovial fluid (SF) of 23 joints whose SF contained these crystals and 33 joints without crystals. The SF originated from 25 joints each of patients with rheumatoid arthritis (RA) and primary osteoarthritis (OA) and 10 patients with various other inflammatory joint diseases. RESULTS: There was significant correlation between citrate concentrations in the SF and plasma with values globally twice as high in the SF as in the plasma. Citrate concentrations in the SF of patients whose SF contained CPPD crystals and/or apatite-like material were not significantly lower than those without crystals. On the other hand, citrate concentrations were significantly lower in the SF of patients with RA and other inflammatory joint diseases versus those with OA. CONCLUSION: We have no evidence that lower amounts of citrate in SF favor the presence of CPPD crystals or apatite-like material. Our results, however, do suggest a complex regulation of the citrate concentration in SF where cellular metabolic processes and citrates arising from the plasma and neighboring tissues probably interact to produce the levels recorded.