In species with a carotid rete, the arterial blood destined for the brain can be cooled on its passage through the rete. The temperature difference between the blood before the rete and the brain is termed selective brain cooling (SBC). The onset and degree of cooling depend on internal body temperature. The aim of this study was to determine the brain sites where the temperature signals driving SBC are generated. Thirty-six experiments were performed in three conscious goats, which were prepared with an arteriovenous shunt, carotid loops, and hypothalamic thermodes to manipulate the temperatures of the trunk (Ttr), the hypothalamus (Thyp), the extrahypothalamic brain (Texh), or the whole brain (Tbr). In all experiments, Ttr was clamped at 39.5 degrees C. The increase of SBC was 2.1 degrees C per 1 degree C increase of Tbr (gain = 2.1). The rise of Thyp at constant Texh yielded a gain of 1.6, whereas the gain of Texh at constant Thyp was 0.7. It is concluded that onset and degree of SBC are predominantly determined by temperature signals generated in the hypothalamus itself.