Systemic hypoxia [PaO2 27.3 +/- 1.8 (SE) mmHg] in anesthetized paralyzed rats reversibly increased within seconds the arterial pressure and activities of the sympathetic nerves and the reticulospinal vasomotor neurons of the rostral ventrolateral medulla (RVL). After peripheral chemodenervation, hypoxia also increased activity of the sympathetic nerves and doubled discharges of the vasomotor neurons while inhibiting a majority of the RVL respiratory neurons. Systemic hypercapnia was not effective in eliciting sympathoexcitatory responses. Iontophoresis of sodium cyanide stimulated the vasomotor and inhibited the respiratory neurons. In contrast, iontophoreses of H+, HCO3-, and lactate were without effects on activity of the vasomotor neurons. We conclude 1) hypoxia excites the vasomotor neurons by activating the arterial chemoreceptors and by activating intrinsic cellular mechanisms probably unrelated to accumulation of metabolic byproducts; 2) hypoxia may be the adequate stimulus exciting the RVL-spinal vasomotor and inhibiting the respiratory neurons during the cerebral ischemic response; and 3) these vasomotor neurons may be central oxygen detectors.