The detailed mRNA distributions of pituitary adenylyl cyclase-activating polypeptide (PACAP) and its selective type I receptor (PAC(1)) were systematically compared in the brain of the frog Xenopus laevis. PACAP mRNA expression overlapped with that of PAC(1) in many brain areas such as the pallium, hypothalamic preoptic area, ventral hypothalamic nuclei, habenular nucleus, most thalamic nuclei, the cerebellular nucleus, and nuclei of isthmi. In some structures, PACAP and PAC(1) gene transcripts were present in anatomically distinct cell layers. For example, in the olfactory bulb, PACAP mRNA was present in the mitral cell layer, whereas gene transcripts for the receptor were observed in the granule layer. In a number of regions, expression showed no obvious overlap. PAC(1) but not PACAP mRNA was present at moderate levels in the Purkinje cell layer of the cerebellum and distal lobe of the pituitary. Conversely, PAC(1) gene expression was absent in the spinal cord while PACAP mRNA signals were observed in the medial portion of the ventral horn and deep portion of the dorsal horn. The granule and molecular cell layer of the cerebellum, alpha-motor neurons in the spinal cord, and reticular nucleus of isthmi showed neither PACAP nor PAC(1) gene transcripts. These localized patterns of ligand and receptor gene expression suggest possible PACAP projection and target fields in the frog brain.