Expression of the inducible transcription factor c-Fos was mapped in mouse brain to identify neural circuits selectively involved in response to cold and hot external temperatures. Male C57BL/6J mice were exposed acutely or repeatedly (seven sessions) to 10 or 34 degrees C in sound-attenuated chambers. Control mice were acclimated to exposure to the experimental room at 20 degrees C. All animals were sacrificed at 90 min for immunohistochemical analysis. A statistically significant induction of c-Fos was observed in the shell of nucleus accumbens and posterior medial cortical amygdala only following the acute thermal exposure, showing a significant habituation of the response to repeated treatments, a finding arguing against specificity of responses in these nuclei to thermal exposures. In contrast, expression of c-Fos was significantly increased following both acute and repeated thermal exposures in subregions of hypothalamus (the median and medial preoptic nuclei, the paraventricular nucleus of hypothalamus and the posterior hypothalamic area), septum (the ventral and dorsal portions of the lateral septum), midbrain (the periaqueductal gray and the intermediate layers of superior colliculus), as well as in the dentate gyrus and the paraventricular nucleus of thalamus, suggesting specificity of their responses to external temperatures. Expression of c-Fos was also significantly increased in the Edinger-Westphal nucleus following acute thermal exposures versus control mice, but not versus mice repeatedly exposed to cold and hot temperatures, providing modest support for thermal specificity of c-Fos response in this nucleus. While thermal sensitivity of hypothalamic structures has been previously confirmed by many authors, the present study identifies a number of structures previously not found to be responsive to changes in external temperature, and lays ground for future work important for identification of neural circuits involved in thermoregulation.