Activation of renal sympathetic nerve activity (RSNA) has not been observed during long-term infusion of angiotensin II (AngII) which results in marked hypertension, despite activation of hypothalamic autonomic regions. We examined whether the function of central pathways influencing sympathetic activity is altered in conscious rabbits given a low dose of AngII that produces a modest hypertension and, therefore, limited secondary complications. METHODS: Rabbits received AngII (20-30 ng/kg per min, subcutaneously) or sham treatment for 3 months at which time they were implanted with a renal sympathetic nerve electrode and the responses to airjet stress, baroreflexes and hypoxia were examined. RESULTS: AngII infusion for 3 months increased mean arterial pressure by 16 and RSNA by 43 . Increases in RSNA during airjet stress and hypoxia (10 O2) were 35 and 65 greater in AngII-treated rabbits than sham controls, respectively. Tachycardic responses were also enhanced. Baroreflexes were shifted to the right and upward in the AngII animals but baroreflex gain was similar in the two groups, indicating near complete resetting. Greater neuronal Fos-related antigen immunoreactivity was found in the vascular organ of the lamina terminalis, paraventricular and supraoptic hypothalamic nuclei in AngII-treated rabbits compared with sham. CONCLUSION: Our results suggest that low-dose AngII-treatment results in marked sympathetic activation at rest and during stress and hypoxia, due to activation of specific hypothalamic pathways. These mechanisms may contribute to sympathetic activation in conditions associated with chronic activation of the renin-angiotensin system such as obesity or renovascular disease.