To test the hypothesis that arginine vasopressin (AVP) in the cerebral spinal fluid (CSF) influences CSF dynamics at simulated altitudes, cannulae were bilaterally implanted into the lateral ventricles of rabbits and rats. Recordings of CSF pressures at ambient and at various reduced barometric pressures identified an increase in CSF pressure in animals at simulated altitudes. Samples of CSF collected before and immediately after altitude exposures and assayed for AVP did not show a significant change in AVP concentration. Brain water content did not change after 6-8 h of reduced barometric pressure. Intraarterial injections of acetazolamide reduced CSF pressures, whereas intraventricular injection had no effect. Intraventricular angiotensin II (AII) elevated CSF pressures both at ambient (744-755 mm Hg) and reduced barometric pressures. When AII was preceded by saralasin, an AII blocker, the rise in CSF pressure with AII injection was prevented. Indeed, saralasin given alone, reduced or prevented the rise in CSF pressure seen at simulated altitudes. Intraventricular AVP did not influence CSF pressures nor did prostaglandins E2 and F1 alpha and norepinephrine. In AVP-deficient (Brattleboro) rats, response to intraventricular AVP depended on barometric pressure; i.e. CSF pressure rose when the rat was exposed to reduced barometric pressures and fell when the rat was exposed to ambient pressure. We suggest that hypobaric stress could cause an increase in AII content of the central nervous system which, in turn, would lead to an increase in CSF pressure. The exact mechanism of CSF pressure increase after AII increase remains to be investigated.