Envenoming by Carukia barnesi may produce life-threatening Irukandji syndrome. There is little published on the activity of C. barnesi venom. This is the first study to investigate the in vivo cardiovascular effects of C. barnesi venom and a tentacle extract (devoid of nematocysts). Venom (50 microg/kg or 100 microg/kg, i.v.) produced a pressor response (42+/-3 and 44+/-6 mmHg, respectively; n=4) and increase in heart rate (31+/-5 and 13+/-2 bpm, respectively; n = 4) in anaesthetised rats. These changes were not dose-dependent and were followed by cardiovascular collapse in one of four rats receiving 50 microg/kg and three of four animals receiving 100 microg/kg. Prazosin (50 microg/kg, i.v.) significantly attenuated the venom (50 microg/kg, i.v.)-induced pressor response (-8+/-3 mmHg; P < 0.05; n = 4) and tachycardia (-9+/-4 bpm; P < 0.05; n = 4). Tentacle extract (100 microg/kg; i.v.) produced a pressor response (51+/-12 mmHg; n = 3) and an increase in heart rate (35+/-1 bpm; n = 3) in anaesthetised rats, with no subsequent cardiovascular collapse. The results of this study are consistent with the effects shown by humans envenomed by C. barnesi which are postulated to be a result of catecholamine release. We show, for the first time, that C. barnesi tentacle extract, free of nematocyst material, produces cardiovascular effects which are distinct from those caused by venom derived from isolated nematocysts.