The effect of tetrodotoxin-induced hypotension on intracranial pressure (ICP) was investigated in cats with normal and artificially increased ICP. Cats were anesthetized with intraperitoneal pentobarbital (25-30 mg/kg), intubated, and ventilated with nitrous oxide in oxygen. Mean arterial pressure (MAP), heart rate (HR), and pulmonary arterial pressure (PAP) were continuously recorded. A double 18-gauge needle was inserted into the cisterna magna; ICP was continuously monitored from one needle and the other was used to increase and maintain ICP at 27 +/- 4 mm Hg by infusion of pH-adjusted Ringer's lactate solution. After control measurements were taken, tetrodotoxin (TTX) was given intravenously in each cat when ICP was normal and increased. Injection of 8-16 micrograms TTX (approximately equal to 2-4 micrograms/kg) decreased MAP 40-50% for 8-12 min under both initial ICP conditions. Whether initial ICP was normal or elevated, no significant increase occurred in ICP (0.6 to 1 mm Hg), and cerebral perfusion pressure (CPP) was not jeopardized. When initial ICP was normal, TTX caused a decrease in HR that was statistically but not clinically significant. The change in HR when initial ICP was increased was not statistically or clinically significant. No significant change in PAP was apparent during TTX-hypotension under either initial ICP condition.