This study examined some of the effects of soldierfish (Gymnapistes marmoratus) venom on the cardiovascular system of rats. Venom (20 microg/ml) produced a biphasic response on rat isolated spontaneously beating atria. This was characterised by a negative, followed by a positive, inotropic and chronotropic action. The increase in force and rate was significantly reduced by propranolol (5 microM) or pretreatment of the rats with reserpine. The decrease in force was significantly inhibited by atropine (0.5 microM). Venom (20-60 microg/ml) produced dose-dependent relaxation in rat isolated endothelium-intact aortae but no response in endothelium-denuded, aortae. Relaxation to venom (30 microg/ml) was significantly inhibited by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (NOLA; 0.1 mM) but was unaffected by atropine (0.5 microM). Venom (200 microg/kg, i.v.) produced a biphasic response in anaesthetized rats, consisting of an initial decrease (phase 1) followed by a prolonged increase (phase 2) in mean arterial pressure. Indomethacin (5 mg/kg, i.v.) significantly inhibited phase 1 of the response to venom and significantly potentiated phase 2. NOLA (30 mg/kg, i.v.) significantly inhibited phase 1 of the response to venom and had no significant effect on phase 2. Propranolol (0.5 mg/kg, i.v.) had no significant effect on phase 1 of the response to venom but significantly potentiated phase 2. Neither phase of the response to venom was significantly affected by atropine (2 mg/kg, i.v.), methysergide (2 mg/kg, i.v.) or prazosin (50 microg/kg, i.v.). These results suggest that soldierfish venom acts indirectly at beta-adrenoceptors to produce a positive inotropic and chronotropic effect in atria, and acts at muscarinic receptors to produce a negative inotropic effect. In addition, beta-adrenoceptors mediate a delayed depressor component in vivo that is absent throughout the initial depressor response to the venom and present during, but masked by, the pressor response. Soldierfish venom also appears to stimulate the release of nitric oxide from endothelial cells to produce relaxation of vascular smooth muscle and contribute to the depressor response produced by the venom in anaesthetized rats. The depressor response also appears to be partially mediated by vasodilator prostanoids.