The central neural pathways for thermoregulation and fever are not well understood. It is known, however, that cutaneous vasoconstrictor nerves such as those to the rat’s tail are under tonic inhibitory control from the preoptic area [1]. Thermoregulatory and febrile control of those vessels is thought to be brought about by variations in the inhibitory tone from preoptic warm-sensitive neurons, acting on sympathetic premotor neurons in the medullary raphé [2]. Recently, however, we identified an excitatory pathway from the preoptic area to the medullary raphé, and found that this mediated the reflex vasoconstrictor response to cooling the skin [3]. We wondered whether that excitatory pathway could also be responsible for the tail vasoconstrictor response in fever. Two types of experiment were performed on urethane-anaesthetised rats (1.4 g/kg i.v), which were artificially ventilated but not paralysed. Experimental fever was induced by Prostaglandin E2 (PGE2), given by microinjection either into the rostromedial preoptic area [1] (0.2ng in 60nl) or into the lateral cerebral ventricle (50ng in 1.5µl). Single or few-unit nerve activity was recorded from tail vasoconstrictor fibres [1, 3]. In the first series, preoptic microinjections of PGE2 were followed by microinjections into the same site of either the inhibitory amino acid, glycine (0.5M, 60nl), or vehicle. Preoptic glycine (but not vehicle) injections roughly halved the tail vasoconstrictor fibre response to preoptic PGE2, suggesting that an excitatory output signal from that region had been blocked. In the second series, the antagonist of ionotropic glutamate receptors, kynurenate (50mM, 120nl), was injected into the medullary raphé. Raphé kynurenate (but not vehicle) injections fully reversed the tail vasoconstrictor fibre response to intra-preoptic or intracerebroventricular injections of PGE2. These findings suggest that in PGE2-induced fever, an excitatory output signal from the preoptic area contributes to the tail vasoconstrictor response. They also show that this response depends entirely on excitatory (ionotropic glutamatergic) neurotransmission in the medullary raphé. Directly or indirectly, therefore, a descending excitatory pathway from the preoptic area mediates rat tail vasoconstrictor responses to experimental fever. These findings alter our understanding of thermoregulatory mechanisms in fever. It remains to be shown whether fever uses the same descending excitatory pathway that mediates tail vasoconstrictor responses to cold skin [3].