Vasoactive Intestinal Polypeptide (VIP) exerts its biological effects through interaction with two high affinity receptors named the VIP1- and the VIP2 receptors. Their messenger RNAs have been mapped in rat brain by in situ hybridization. A cyclic peptide (RO 25-1553) and a secretin analogue ([R-16]chicken secretin) were identified as selective agonist peptides for the VIP2- and VIP1 receptors, respectively. The iodinated peptides retained the high affinity and selectivity of the unlabelled peptides and were used for the mapping of each receptor subclass in rat brain. VIP1 receptors were present in the cerebral cortex, the piriform cortex, the claustrum, the caudate-putamen, the dentate gyrus, the lateral amygdaloid nucleus, the anteroventral thalamic nucleus, the rhomboid nucleus, the supraoptic nucleus and the choroid plexus. VIP2 receptors were present in the cerebral cortex: the claustrum, the caudate-putamen, the nucleus accumbens, the lateral septal nuclei, the bed nucleus of the stria terminalis, the basolateral amygdaloid nucleus, the Ammon's horn, the thalamic nuclei except some centromedial nuclei, the medial habenula, the suprachiasmatic nucleus, the periventricular nucleus, the mammilary nucleus, the superior colliculus and the choroid plexus. (C) 1997 Elsevier Science Inc.