OBJECTIVES: A limited retrospective study of patients with rheumatoid arthritis (RA) found that serum phospholipase A2 (PLA2) activity correlates with disease activity. To assess the strength of this relationship we investigated prospectively 25 patients with RA using a double blind approach. METHODS: Twenty five patients who fulfilled the 1987 American College of Rheumatology criteria for RA had clinical and laboratory assessments. PLA2 activity was measured before and after treatment of 3 months in patients with RA. Fourteen healthy individuals were also enrolled as controls. PLA2 activity was assayed using E.coli membrane phospholipid substrate labelled with[14C]-oleic acid. RESULTS: 1) Serum PLA2 activity was significantly higher in patients with RA than that of normal healthy controls (p<0.001). 2) In Patients with RA, synovial fluid PLA2 activity was higher than serum PLA2 activity, and a positive correlation between PLA2 in synovial fluids and matched sera was found in these patients (p<0.05). 3) After treatment, PLA2 activity was significantly decreased with improvement of clinical(morning stiffness and Ritchie index) and laboratory(ESR, CRP and rheumatoid factor)assessments (p<0.001). 4) Among the clinical and laboratory markers of disease activity, ESR showed the best correlation with serum PLA2 activity (r=0.493, p<0.05). 5) In the patients who did not respond clinically to treatment (n=5), there was no significant decrease in PLA2 activity. CONCLUSION: PLA2 activity significantly correlates with RA activity and may serve as an index of disease activity in RA.