The expression pattern of mRNA encoding two orexin receptors (OX₁R and OX₂R) in the rat brain was examined. OX₁R and OX₂R exhibited marked differential distribution. Within the hypothalamus, OX₁R mRNA is most abundant in the ventromedial hypothalamic nucleus whereas OX₂R is predominantly expressed in the paraventricular nucleus. High levels of OX₁R mRNA were also detected in tenia tecta, the hippocampal formation, dorsal raphe, and locus coeruleus. OX₂R mRNA is mainly expressed in cerebral cortex, nucleus accumbens, subthalamic and paraventricular thalamic nuclei, anterior pretectal nucleus. The presence of orexin receptor mRNA in the hypothalamus is in support of its proposed role in feeding regulation. Broad central distribution of orexin receptors may indicate additional functions for orexins.