The distribution of prolactin receptors (PRL-R) in the rat brain was investigated for the first time with the immunohistochemical technique using monoclonal antibodies raised against PRL-R purified from rat liver. Granular immunostaining was observed in neurons and along their dendritic processes and fibers. PRL-R like immunoreactive neurons were found in a number of brain areas. There was a very dense labelling in the cerebral cortex (pyramidal cell layer), septal nuclei, amygdaloid complex as well as in the hypothalamus (suprachiasmatic, supraoptic, paraventricular and dorsomedial nuclei). A dense staining was seen in the substantia nigra, habenula and in the paraventricular thalamic nucleus. Immunostaining was also found in the choroid plexus and in the subcommissural organ. Comparison between the present distribution and that of PRL-like immunoreactivity indicates that the density of PRL-R generally corresponds to that of the fibers. However, in some regions densely stained by PRL-R antibody, there are very few PRL-immunoreactive fibers. These results are suggestive of different modes of action of PRL in the brain.