Leptin, a hormone secreted from the adipose tissue, is involved in the regulation of food intake and neuroendocrine function, by modulation of the expression and/or function of various neuropeptides in the hypothalamus. The long isoform (OB-Rb) is the major signaling form of the leptin receptor in the hypothalamus. We have used double-labeling immunohistochemistry to examine the extent of OB-Rb expression in neurochemically defined cell types in the ovine hypothalamus. OB-Rb-like immunoreactivity was widespread within cells localized to the periventricular, paraventricular, supraoptic, dorsomedial hypothalamic, ventromedial hypothalamic and arcuate nuclei, as well as the median eminence, perifornical, anterior hypothalamic and lateral hypothalamic areas and the zona incerta. Double-labeling showed expression of OB-Rb in 59.6+/-6.0% neuropeptide Y-containing cells, 60.8+/-4.7% galanin-containing cells, 89.8+/-2.65% pro-opiomelanocortin-containing cells, 73.4+/-3.5% tyrosine hydroxylase-containing cells and 31.8+/-2.8% corticotropin-releasing factor-containing cells. Interestingly 100% of melanin-concentrating hormone and orexin positive cells were also OB-Rb immunoreactive. These data provide semi-quantitative information on the extent to which various cell types express OB-Rb in the hypothalamus. Expression of OB-Rb within specific neuropeptidergic neurons provides evidence for the direct action of leptin upon the various neurochemical systems that regulate food intake, neuroendocrine and autonomic function in the brain.