Chronic intermittent hypoxia (CIH) increases mean arterial pressure (MAP) and FosB/FosB staining in central autonomic nuclei. To test the role of the brain renin-angiotensin system (RAS) in CIH hypertension, rats were implanted with intracerebroventricular (ICV) cannulae delivering losartan (1ug/h) or vehicle (VEH) via mini-osmotic pumps and telemetry devices for arterial pressure recording. A third group was given the same dose of losartan subcutaneously (SC). Two groups of losartan treated rats served as normoxic controls. Rats were exposed to CIH or normoxia for 7 days then sacrificed for immunohistochemistry. ICV losartan attenuated CIH-induced increases in arterial pressure during CIH exposure (0800-1600 during the light phase) on days 1, 6, and 7 and each day during the normoxic dark phase. FosB/FosB staining in the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO), paraventricular nucleus of the hypothalamus (PVN) the rostral ventrolateral medulla (RVLM) and the nucleus of the solitary tract (NTS) was decreased in ICV losartan treated rats. SC losartan also reduced CIH hypertension during the last two days of CIH and produced bradycardia prior to the effect on blood pressure. Following SC losartan, FosB/FosB staining was reduced only in the OVLT, MnPO, PVN, and NTS. These data indicate that the central and peripheral RAS contribute to CIH-induced hypertension and transcriptional activation of autonomic nuclei and that the contribution of the central RAS is greater during the normoxic dark phase of CIH hypertension.