Objective: To measure the activity of phospholipase A(2) (PLA(2)) in peripheral blood mononuclear cells (PBMC), polymorphonuclear leukocytes (PMN) and platelets in patients with rheumatoid arthritis (RA) before and during treatment with methotrexate (MTX). Methods: Nine patients with RA treated with MTX were studied for six months. PBMC, PMN, and platelets were isolated at baseline and at monthly intervals thereafter PLA(2) activity was measured in lysates of the various cell fractions by the hydrolysis of radiolabeled lysocholine from phosphatidylcholine, L-Dipalmitoyl using thin layer chromatography. Data were calculated as pmol of C-14 choline released per hour per milligram of cellular protein. Results: At baseline, compared to normal controls, PLA(2) activity was significantly increased in platelets (p = 0.02) brit not in PBMC (p = 0.32) nor in PMN (p = 023). Seven of the nine patients responded clinically to treatment with MTX. In these 7 patients over the six-month treatment course, there was a significant decrease in PLA(2) activity iri! the platelets which correlated with improvement in disease activity (R = 0.82, p = 0.03). PLA(2) activity also decreased in PBMC and PMN, but the correlation with disease improvement was not statistically significant (R = 0.71, p = 0.07 for PBMC; and R = 0.43, p = 0.33 for PMN). Conclusion. PLA(2) activity in platelets but not in PBMC or PMN is significantly increased in patients with RA compared to normal controls. Although PLA(2) activity decreased in all the cells during treatment with MTX, only PLA(2) activity in platelets correlated significantly with improvement in disease activity.