The rat paw edema-inducing, acute inflammatory activity of four snake venom phospholipase A2S (PLA2) (Naja naja, Naja mocambique mocambique, Crotalus atrox and recombinant Naja naja naja) and of recombinant human type II PLA2 (rh-PLA2) found in rheumatoid synovial fluid, were compared after a bolus subplantar injection. The snake venom-derived PLA2s, including the recombinant Naja naja naja, were potent inducers of paw edema. On the other hand, when given in similar amounts (protein and/or enzymatic activity), the rh-PLA2 did not produce paw edema. Furthermore, the addition of Naja naja PLA2, blood plasma from rats with adjuvant arthritis or the E. coli-based enzymatic incubation mixture used to measure PLA2 activity to the injection mixture containing rh-PLA2, did not result in paw edema-inducing activity. These results suggest that the lack of paw edema-inducing activity of rh-PLA2 may be due to significant structural differences between snake venom PLA2s and human PLA2 which allow snake venom PLA2s, but not the human group II PLA2, to express inflammatory activity as measured by paw edema in rat induced by a bolus injection.