Using a non-radioactive in situ hybridization detection method, we found that fasting up-regulated leptin receptor mRNA expression in the brain of C57 Bl/6 lean (+/+) but not obese (ob/ob) mice. After the lean mice were fasted for 24 h, increased leptin receptor mRNA expression was found in the arcuate and ventromedial hypothalamic nuclei, medial habenular nucleus and dentate gyrus of hippocampal formation. There was only a minor increase in mRNA expression of leptin receptor in the hippocampus proper while the piriform cortex remained unchanged. However, after the obese mice were fasted for 24 h, no detectable changes of leptin receptor mRNA expression could be found. These results indicated that leptin receptor gene expression was influenced by nutritional status. Further, genetically obese mice showed an inability to respond to nutritional change, probably due to the fact that obese mice lack leptin.