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Bothropstoxin-I and bothropstoxin-II are phospholipase A₂ homologues isolated from Bothrops jararacussu snake venom. The former is devoid of phospholipase A₂ activity whereas the latter has very low enzymatic activity. In this study, we have investigated the in vivo (rat paw and skin oedema) and in vitro (mast cell degranulation) inflammatory effects caused by bothropstoxin-I and bothropstoxin-II. Bothropstoxin-I (25–100 μg/paw) and bothropstoxin-II (12.5–50 μg/paw) caused dose-dependent rat paw oedema. The intradermal injection of bothropstoxin-I (0.125–5 μg/site) and bothropstoxin-II (0.125–5 μg/site) into rat skin also resulted in dose-dependent oedema formation. These oedematogenic activities were largely reduced in animals pretreated with the histamine/5-hydroxytryptamine (5-HT) receptor antagonist cyproheptadine (2 mg/kg, i.p. 0.5 h before). Similarly, p-bromophenacyl bromide, a compound …