Pancreatic polypeptide (PP) is a regulatory peptide that modulates gastrointestinal function. Previously we demonstrated PP receptors in the brainstem and interpeduncular nucleus, and the PP receptors in the brainstem appear to modulate gastric motility and pancreatic exocrine secretion. The purpose of this study is to extend our understanding of the distribution of PP receptors in the rat brain in order to determine the systems that are potentially modulated by PP. Rat brains were studied using 125I-PP receptor autoradiography on cryostat sections of the entire brain cut in three planes (horizontal, sagittal, and coronal). Brain regions exhibiting PP binding sites were confirmed when identified in all three planes of section. Saturable PP binding was identified in the hypothalamus (arcuate and paraventricular n), the rostral forebrain (medial preoptic area, anterior olfactory nucleus, islands of Calleja, the dorsal endopiriform n, piriform cortex, and the bed n of the stria terminalis), medial amygdaloid n; the thalamus (anteromedial thal. n; reuniens thal. n; and paraventricular thal n), the interpeduncular red nucleus, substantia nigra, parabrachial n; locus coeruleus, mesencephalic trigeminal n, dorsal motor n of the vagus, the n solitary tract, and the area postrema. We conclude that PP receptors are distributed widely throughout the rat brain. The distribution of many of these PP binding sites corresponds to brain regions regulating digestion and autonomic function. We speculate, based on the patterns of binding in the olfactory and limbic systems, that PP receptors might be involved in positive reinforcement of ingestion behavioral as well as modulation of gastrointestinal function.