The changes induced in the mean arterial blood pressure of anaesthetised rats following the administration of armed spider ( Phoneutria nigriventer) venom have been investigated. The intravenous injection of Phoneutria nigriventer venom (0.1 mg/kg) evoked a brief and reversible decrease in the mean arterial blood pressure whereas a higher dose of venom (0.3 mg/kg) caused a biphasic response characterized by a short-lasting hypotension followed by a sustained and prolonged hypertension (40–50 min). These changes were accompanied by tachycardia, salivation, fasciculations, defecation and respiratory disturbances. Pretreatment of the animals with atropine (10 mg/kg), propranolol (100 mg/kg), phenoxybenzamine (100 mg/kg) and indomethacin (4 mg/kg) did not significantly affect the mean arterial blood pressure changes induced by Phoneutria nigriventer venom. Similarly, the bradykinin B 2 receptor antagonist Hoe 140 ( d-Arg-[Hyp 3,Thi 5, dTic 7,Oic 8]-bradykinin) (0.6 mg/kg), the PAF receptor antagonist WEB 2086 (3-(4-(2-chlorophenyl)-9-methyl-6 H-thieno-(3,2 f) (1,2,4)-triazolo-(4,3- a) (1,4)-diazepine-2-yl)-(4-morpholinyl)-1-propanone) (20 mg/kg), the tachykinin NK 1 receptor antagonist SR 140333 (( S)1-{2-[3-(3,4-dichlorophenyl)-1-(3-iso-propoxyphenyl acetyl) piperidin-3-yl] ethyl}-4-phenyl-1-azoniabicyclo[2.2.2] octane, chloride) (0.5 mg/kg), the tachykinin NK 2 receptor antagonist SR 48968 ( (S)-N-methyl- N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide) (0.5 mg/kg) and the nitric oxide synthase inhibitor N ω-nitro- l-arginine methyl ester (10 mg/kg) had no significant effect on the mean arterial blood pressure changes induced by Phoneutria nigriventer venom. The increase in the blood pressure induced by Phoneutria nigriventer venom was also not significantly affected by either the angiotensin II receptor antagonist losartan (10 mg/kg) or the endothelin ET A receptor antagonist FR 139317 (( R)2-[( R)-2-[[1-(hexahydro-1 H-azepinyl]carbonyl]amino-4-methyl-pentanoyl]amino-3-[3-(1-methyl-1 H-indoyl)]propionyl] amino-3-(2-propionyl] amino-3-(2-pyridyl) propionic acid) (30 mg/kg). The ATP-dependent K + channel antagonist glibenclamide (50 mg/kg) reduced by 40% the hypotension induced by Phoneutria nigriventer venom without affecting the hypertensive response. Pretreatment of the animals with L-type Ca 2+ channel antagonists such as verapamil (10–100 μg/kg/min), diltiazem (40–120 μg/kg/min) and nifedipine (0.3–10 mg/kg) markedly attenuated the hypertension induced by Phoneutria nigriventer venom. Verapamil (30 μg/kg/min) and diltiazem (120 μg/kg/min) also promptly reversed the established hypertension induced by Phoneutria nigriventer venom when infused 8 min after venom injection. Our results indicate that the brief decrease of blood pressure induced by Phoneutria nigriventer venom is partially due to ATP-dependent K + channel activation. The prolonged hypertension seems to result from direct Ca 2+ entry into vascular and/or cardiac muscles.