The distribution of the kappa opioid receptor mRNA in adult mouse brain has been determined using the technique of in situ hybridization histochemistry. The mRNA for the kappa opioid receptor was expressed in distinct areas throughout the brain. The telencephalon showed high levels of expression in the deeper layers of the parietal and temporal cortex, olfactory tubercle, nucleus accumbens, claustrum, endopiriform nucleus, nucleus of the vertical and horizontal limb of the diagonal band, and medial and central nuclei of the amygdala. In the diencephalon, kappa opioid receptor mRNA was present in multiple medial thalamic nuclei including the centromedial, paraventricular, parafasicular, central, and peritenial nuclei, as well as in most hypothalamic nuclei including the ventromedial, periventricular, supraoptic, arcuate, and dorsomedial nuclei. The mesencephalon showed highest levels of kappa receptor mRNA in the substantia nigra pars compacta, ventral tegmental area, zona incerta, interpeduncular nucleus, superior colliculus, inferior colliculus, central grey, and the raphe nucleus. In the metencephalon, kappa opioid receptor mRNA was expressed in the parabrachial nuclei, locus coeruleus, dorsal and ventral tegmental nuclei, and the raphe pontine nuclei. The distribution of the kappa receptor mRNA closely coincides with the localization of binding sites in rat brain for [3H]U-69,593, a specific kappa 1 opioid receptor ligand. The mRNA distribution also correlates with neuroanatomical sites of actions of kappa agonists and distribution of the endogenous kappa receptor ligand dynorphin.