Using a new technique to extract venom from the nematocysts, the efficacy of CSL box jellyfish antivenom (AV) and adjunct therapies, verapamil and magnesium sulfate (MgSO(4)), were investigated against the in vivo cardiovascular effects of Chironex fleckeri venom in anaesthetised rats. C. fleckeri venom (30 microg/kg; i.v.) produced a transient hypertensive response followed by hypotension and cardiovascular collapse within 4 min of administration. Prophylactic treatment of anaesthetised rats with CSL box jellyfish AV (3000 U/kg; i.v.) did not have any effect on the venom-induced pressor response, but prevented cardiovascular collapse in four out of 10 animals. Administration of verapamil (20mM@0.25 ml/min; i.v.) either alone or in combination with AV, did not have any effect on the C. fleckeri venom-induced pressor response nor the consequent hypotension or cardiovascular collapse of animals. However, the administration of verapamil negated the partially protective effects of AV. Concurrent artificial respiration of animals with the above treatments did not attenuate the C. fleckeri venom-induced cardiovascular effects. MgSO(4) (0.05-0.07M@0.25 ml/min; i.v.) alone did not have any effect on the venom-induced pressor response nor the consequent cardiovascular collapse of animals. However, although combined AV and MgSO(4) administration could not inhibit the transient pressor effect following the administration of C. fleckeri venom, it prevented cardiovascular collapse in all animals. We show for the first time, the cardiovascular effects of a C. fleckeri venom sample free of tentacular contamination and the potential of MgSO(4) as an adjunct therapy for the treatment of potentially fatal C. fleckeri envenomings.