The adipocyte-derived hormone, leptin, and its receptor, are now known to be integral components of a physiological signalling system that regulates fuel stores and energy balance. Constitutive leptin expression has been demonstrated only in adipose tissue, placenta and stomach. We have used RT-PCR to show that leptin mRNA is selectively transcribed in specific areas of rat brain and pituitary, and in a rat glioblastoma cell line. Using immunocytochemistry we have also shown leptin protein immunoreactivity in the corresponding tissues and cells, and confirmed this by Western blot using two epitope-specific antisera. Leptin mRNA expression in the hypothalamus is suppressed by fasting (48hr), suggesting a role for brain leptin in the central regulation of appetite. These data support the hypothesis that central nervous system derived leptin is a likely ligand for central leptin receptors.