We recently identified a somatosensory pathway that transmits temperature information from the skin to a median subregion of the preoptic area (POA), a thermoregulatory centre. Here, we investigated in vivo the local neuronal circuit in the rat POA that processes the thermosensory information and outputs thermoregulatory effector signals. Skin cooling-evoked increases in sympathetic thermogenesis in brown adipose tissue, in metabolism and in heart rate were reversed by inhibition of neurons in the median preoptic nucleus (MnPO). Glutamatergic stimulation or disinhibition of MnPO neurons evoked thermogenic, metabolic and cardiac responses that mimicked the cold-defensive responses to skin cooling and were reversed by antagonizing GABA(A) receptors in the medial preoptic area (MPO), which is thought to contain neurons providing thermoregulatory output to effectors. These results suggest that GABA inhibition of output neurons in the MPO by MnPO neurons that are activated by cool sensory signals from the skin is a core thermoregulatory mechanism within the POA that is essential for the feedforward defence of body temperature against cold challenges in the environment.