Hypoxia evokes a regulated decrease in deep body temperature (Tb). Hydrogen sulfide (H2S), a signaling molecule that belongs to the gasotransmitter family, has been demonstrated to participate in several brain-mediated responses. Rostral ventrolateral medulla (RVLM) is a brainstem region involved in thermoregulation. Recently, it has been shown that exogenous H2S modulates RVLM activity. In the present study, we investigated whether endogenously produced H2S in the RVLM plays a role in the control of hypoxia-induced hypothermia. Tb was measured before and after bilateral microinjection of aminooxyacetate (ADA, 0.2, 1 and 2 pmol/100 nl, a cystathionine S-synthase, CBS, inhibitor) or vehicle into the RVLM followed by a 60-min normoxia (21% inspired O-2) or hypoxia (7% inspired O-2) exposure. Microinjection of AOA or vehicle did not change Tb during normoxia. Exposure to hypoxia evoked a typical decrease in Tb. Microinjection of AOA (2 pmol) into the RVLM followed by hypoxia significantly attenuated the decrease in Tb. Thus, endogenous H2S in the RVLM seems to play no role in the maintenance of basal Tb, whereas during hypoxia this gas plays a cryogenic role. Moreover, RVLM homogenates of rats exposed to hypoxia exhibited a decreased rate of H2S production. Our data are consistent with the notion that during hypoxia H2S synthesis is diminished in the RVLM facilitating hypothermia. (C) 2014 Elsevier Inc. All rights reserved.