Orexin neurons, located in perifornical hypothalamus (de lecea et al., 1998; Sakurai et al., 1998), influence appetite, the sleep-wake cycle, locomotor activity as well as a number of physiological variables. Transgenic mice with ataxin3-mediated destruction of orexin neurons have attenuated thermogenic and other autonomic responses to arousing environmental stimuli (Zhang et al., 2010), but constriction of the tail artery in response to alerting stimuli has not been assessed in animals in which orexin-containing neurons have been selectively destroyed. We have now assessed sympathetic cutaneous vasomotor alerting responses (SCVARs, de Menezes et al., 2009) in the tail artery of conscious unrestrained transgenic Sprague Dawley rats with ataxin3-mediated destruction of orexin neurons (Beuckmann et al., 2004), in comparison with wildtype control animals. Under inhaled isoflurane (2% in oxygen) anaesthesia, transgenic (n=10) and wildtype (n=8) male rats (300-450 g) were instrumented with ultrasound Doppler flow probes (Iowa Inc, USA) chronically implanted around base of the tail artery. All surgical procedures were performed in accord with the Animal Welfare Ethics Committee of Flinders University. Tail probe cables were passed subcutaneously and connected to a headpiece fixed to the skull with dental cement. After one-week recovery unrestrained rats were placed in a quiet closed wooden box at 24-26°C. The tail artery blood flow signal (40 Hz sampling rate) was recorded, via a swivel device, with PowerLab (ADInstruments). We administered standardized alerting stimuli (salient but not stressful) and assessed the acute effect on blood flow in the tail artery, calculated as the percentage change in flow induced by the stimulus (SCVAR index). Group SCVAR results (mean ± SEM) were analysed with factorial ANOVA. The SCVAR index in transgenic rats was 69 ±2%, significantly less than 84±2% (p<0.001), the corresponding wildtype value. Immunohistochemical examination of the perifornical area of the hypothalamus documented complete absence or substantial loss of orexin-containing neurons in the transgenic rats. Our findings support the view that the orexin-containing neurons function to increase the physiological response to the animal’s perception of salient, potentially threatening environmental events.