Nucleus raphe magnus (NRM) is one of the cellular groups of the brainstem that is involved in the physiologic responses to hypoxia and contains nitric oxide (NO) synthase. In the present study, we assessed the role of NO pathway in the NRM on the hypoxic ventilatory response (HVR) and anapyrexia (a regulated decrease in body temperature). To this end, pulmonary ventilation (VE) and body temperature (Tb) of male Wistar rats were measured before and after microinjection of N-monomethyl-L-arginine (L-NMMA, a nonselective nitric oxide synthase inhibitor, 12.5 microg/0.1 microl) into the NRM, followed by hypoxia. Control rats received microinjection of saline. Under resting conditions, L-NMMA treatment did not affect pulmonary VE or Tb. Typical hypoxia-induced hyperventilation and anapyrexia were observed after saline treatment. L-NMMA into the NRM reduced the HVR but did not affect hypoxia-induced anapyrexia. In conclusion, the present study indicates that NO in the NRM is involved in HVR, exerts an inhibitory modulation on the NRM neurons but does not mediate hypoxia-induced anapyrexia.