Cardiotoxin, isolated from Naja naja atra venom, induced rat hind-paw oedema. This effect was suppressed by the pretreatment with dexamethasone or BW 755C, or subplantar co-injection with FPL 55712. Pretreatment with aspirin alone did not affect this response, while a significant reduction of cardiotoxin-induced paw oedema was achieved with aspirin in combination with diphenhydramine and methysergide. Subplantar co-injection of PAF antagonist, BN 52021 or L 652731, with cardiotoxin had no effect on paw oedema, whereas superoxide dismutase/catalase reduced this oedematous response. Cardiotoxin-induced paw oedema was also suppressed by pretreating the rats with isoprenaline. Pretreatment with rat anti-platelet plasma, which greatly reduced peripheral platelet count, did not affect cardiotoxin-induced paw oedema. Cardiotoxin did not trigger platelet aggregation or release reaction either in platelet-rich plasma or in washed platelet suspension. The oedematous response after subplantar co-injection of cardiotoxin with basic or acidic phospholipase A2 appeared to be only an additive effect. These results suggest that arachidonate metabolites, in which leukotrienes are most important, participated in cardiotoxin-induced paw oedema. Superoxide radical was also involved, while PAF and platelets showed little influence in this oedema effect.