Phospholipase A2 (PLA2) from cobra (Naja naja) venom and PLA2 from porcine pancreas accelerated IgE antibody-mediated histamine release from rat peritoneal mast cells. These enhancements were clearly abrogated by heating the enzymes and pretreatment with parabromophenacyl bromide, mepacrine and antiflammin. Indomethacin (cyclooxygenase inhibitor) and AA-861 (lipoxygenase inhibitor) did not affect the enhancement by PLA2. These results indicate that extracellular PLA2 enhances the IgE antibody-mediated histamine release from rat peritoneal mast cells without the participation of arachidonate.