Expression of the leptin receptor gene has been examined in mouse hypothalamus and other brain regions by in situ hybridization. With a probe recognizing all the known splice variants, receptor mRNA was evident in several brain regions (cortex, hippocampus, thalamus), with strong expression in the hypothalamus (arcuate, ventromedial, paraventricular and ventral premammillary nuclei), choroid plexus and leptomeninges. A probe specific to the long splice variant of the leptin receptor (Ob-Rb), containing the putative intracellular signaling domain, again revealed strong expression in the hypothalamus; there was, however, minimal hybridization to choroid plexus and leptomeninges. These results indicate that the hypothalamus is a key site of leptin action, although other brain regions are also targeted.