The inflammaogenic action of four extracellular phospholipases A2 was tested in the rat paw oedema model. Subplantar injection of microgram amounts of the venom phospholipases A2 from Vipera russeli, Naja mocambique mocambique and honey bee, or the porcine enzyme produced a rapid but transient oedematous response. The venom enzyme from Vipera was the most potent in this respect, the pancreatic enzyme the least. Pretreatment of the enzymes with para-bromophenacylbromide profoundly inhibited the ability of the enzymes to produce oedema. The inflammatory response produced by the phospholipases was insensitive to indomethacin, BW755C or the LTD4 antagonist L649,923 but was inhibited by the local administration of methysergide or, by pretreatment of the rats with dexamethasone. The PAF-antagonist BN 52021, but not WEB2086, was an effective inhibitor. Degranulation of mast cells seem the most likely explanation for the inflammatory action of these enzymes in the rat paw.