Uncoupling protein-2 (UCP2) is expressed in large amounts in several tissues. In the mouse brain, in situ hybridization studies have revealed an abundant expression of UCP2 mRNA in the ventral septal region, the hypothalamus, the hindbrain (medulla), the ventricular regions and the cerebellum. In the hypothalamus, a very highly intense hybridization signal is apparent in the suprachiasmatic nucleus, in the medial parvicellular and magnocellular lateral parts of the paraventricular hypothalamic nucleus, and in the arcuate nucleus. In the brainstem, UCP2 is found to be strongly expressed in the dorsal motor nucleus of the vagus nerve. The expression of UCP2 mRNA is also clearly noticeable in the choroid plexuses and in the cerebellum. The expression of UCP2 mRNA in specific regions of the brain as well as its presence in neurons with a known chemical identity suggest that UCP2 mRNA is expressed in neurons. It is as yet premature to conclude about a specific function of UCP2 in the brain. The brain distribution pattern of its transcript suggests that this mitochondrial protein could be part of neuronal circuitries involved in the control of neuroendocrine functions and autonomic responses. Assuming that the UCP2 mRNA encodes a functional uncoupling protein, it can be argued that UCP2 contributes to the metabolic rate and thermoregulation of the neuronal structures to which it is associated. In addition, by elevating oxygen consumption in the brain, UCP2 could in specific regions control the production of reactive oxygen species and thereby influence the process of neural degeneration.