The aim of the present study was to investigate previously suggested adrenergic and tachykinin activity, as well as the cardiovascular effects, of venom from the stonefish (Synanceja trachynis). Stonefish venom (60-120 μg/kg, i.v.) produced dose-dependent bronchoconstriction in anaesthetised guinea-pigs. This response (100 μg/kg, i.v.) was significantly reduced by the neurokinin 1 (NK1) receptor antagonist CP-99,994 (1 mg/kg, i.v.). Contractile responses to venom (4 μg/ml) of guinea-pig isolated ileum (GPI) were significantly inhibited by a combination of the sodium channel blocking drug tetrodotoxin (1 μM) and the ganglion blocking drug mecamylamine (10 μM). However, subsequent administration of CP-99,994 (0.1 μM) did not produce further inhibition. Endogenous tachykinin depletion with capsaicin (1 μM) also significantly attenuated responses to venom (4 μg/ml) in GPI. Venom (4 μg/ml) produced increases in rate and force of contraction of rat spontaneously beating isolated atria which were significantly inhibited by the β-adrenoceptor antagonist propranolol (5 μM) but not by noradrenergic transmitter depletion with reserpine (4.5 mg/kg, i.p.). In the presence of the α1-adrenoceptor antagonist prazosin (0.3 μM), venom (6 μg/ml) significantly inhibited electrically evoked twitches of prostatic segments of rat vas deferens. The inhibitory effect of venom was significantly reduced by the α2-adrenoceptor antagonist idazoxan (1 μM) but not by propranolol (5 μM) or the neurokinin 2 (NK2) receptor antagonist SR-48,968 (0.1 μM). Venom (60-120 μg/kg, i.v.) produced dose-dependent increases in mean arterial blood pressure in anaesthetised rats. This presser response (60 μg/kg, i.v.) was significantly reduced by prazosin (10-50 μg/kg, i.v.) and the leukotriene receptor antagonist SB205312 (1 mg/kg, i.v.), significantly increased by propranolol (2 mg/kg, i.v.), but not significantly affected by the cyclooxygenase inhibitor indomethacin (10 mg/kg, i.v.) or the thromboxane A2/prostaglandin H2 (TP) receptor antagonist GR32191B (1 mg/kg, i.v.). Presser responses to venom (100 μg/kg, i.v.) were also observed in anaesthetised rabbits. These results suggest that stonefish venom contains a component capable of stimulating the release of endogenous tachykinins with subsequent activity at NK1 receptors. The venom also appears to act via stimulation of sodium channels on sensory nerves. The venom also has activity at α2-adrenoceptors and a direct action at β-adrenoceptors. The effect of venom on blood pressure of anaesthetised rats appears to include a presser component that is mediated, in part, by α1-adrenoceptors and leukotriene receptors, and a depressor component that is mediated by β-adrenoceptors. However, the presser response does not involve action at TP receptors, or require the production of cyclo-oxygenase metabolites.