Abstract. Consumptive coagulopathy was induced within 4 h in Atlantic salmon, Salmo salar L., by injecting purified serine protease from Aeromonas salmonicida into the dorsal aorta. Pretreatment with a bolus intravascular injection of (human) antithrombin (AT) or (bovine) α2-macroglobulin (α2M) just prior to injection of the protease alleviated the in vivo pro-coagulant effects of the enzyme, but could not hinder the development of consumptive coagulopathy. In fish receiving only saline as pretreatment, the coagulopathy was evident even after 28h, but the fish were not overtly sick. The addition of the exogenous inhibitors increased the fish's natural protection against the bacterial exotoxin, suggesting that both AT and α2M are of importance for the outcome of the pathologic process. Results further indicate that while AT in vivo was mainly directed against generated thrombin and activated coagulation factor X (FXa), α2M inhibited the protease directly.