This study examined the possible contribution of the brain renin-angiotensin system on the sympathetic activation induced by hypoxia in conscious rabbits. Blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded under conditions of normoxia and hypoxia (10% O2 + 3% CO2) before and after fourth ventricular administration of either losartan (10 micrograms in 25 microliters), enalaprilat (500 ng in 25 microliters) or Ringer's (25 microliters). Hypoxia increased the RSNA by 113% and slightly decreased HR without changing BP. It also increased the variability of BP or HR in the 0.2-0.4 Hz frequency domain. Losartan and enalaprilat did not change the resting BP or HR but elevated the RSNA increase seen during hypoxia. Our results suggest that central angiotensin is involved in mediating response to chemoreceptor activation.