The rostral ventrolateral medullary surface (VMS) plays a major state-dependent role in the control of breathing; its role during hypoxia remains speculative. We therefore assessed activity within the rostral VMS by measuring reflectance of scattered light in 5 goats during normoxia, hypoxia, and hyperoxia in awake and halothane anesthetic states. Within the first minute of hypoxia, light reflectance began to decrease in the awake state; reflectance reached a stable nadir within 30 min about 10 and 17% below control values (P < 0.01), at 12 and 10% inspired O2, respectively. In the anesthetized state, reflectance decreased (P < 0.01) by 6% at 10% inspired O2. After 30 min in the awake state, reflectance returned (P < 0.01) toward control values, reaching a stable level at 7 and 11% below control at 12 and 10% inspired O2, respectively (P < 0.05). Hyperoxia resulted in a 1% increase (P < 0.05) in reflectance. Changes in reflectance during hypoxia did not consistently parallel changes in breathing, heart rate, or arterial blood pressure. We conclude that, a) decreased reflectance during hypoxia results, in part, from increased neural activity, and b) state exerts a substantial effect on the response of VMS areas to hypoxia.