Hypoxia results in decreased arterial P_O2, arterial chemoreflex activation, and compensatory increases in breathing, sympathetic outflow, and neuroendocrine secretions, including increased secretion of vasopressin (AVP), corticotropin releasing hormone (CRH), adrenocorticotropin hormone (ACTH), and corticosterone. In addition to a brainstem pathway including the nucleus tractus solitarius (nTS) and the rostral ventrolateral medulla (RVLM), medullary pathways to the paraventricular nucleus of the hypothalamus (PVN) contribute to chemoreflex responses. Experiments evaluated activation of specific cell phenotypes within the PVN following an acute hypoxic stimulus (AH, 2 hr, 10% O₂) in conscious rats. Retrograde tracers (from spinal cord and RVLM) labeled pre-sympathetic (PreS) neurons; immunohistochemistry (IHC) identified AVP- and CRH-IR cells; Fos- IR was an index of neuronal activation. Hypoxia activated AVP-IR (~ 6%) and CRH-IR (~15%) cells, but not PreS cells in the PVN, suggesting that sympathoexcitation during moderate AH is mediated mainly by a pathway that does not include PreS neurons in the PVN. Approximately 14 to 17% of all PVN cell phenotypes examined expressed nNOS-IR. AH activated only nNOS-negative AVP-IR neurons. In contrast ~ 23% of activated CRH-IR neurons in the PVN contained nNOS. In the median eminence, CRH-IR terminals were closely opposed to tanycyte processes and endfeet (vimentin-IR) in the external zone, where vascular NO participates in tanycyte retraction to facilitate neuropeptide secretion into the pituitary portal circulation. Results are consistent with an inhibitory role of NO on AVP and PreS neurons in the PVN, and an excitatory role of NO on CRH secretion in the PVN and median eminence.