The study of somatostatin receptors by means of autoradiography in tissue sections revealed high densities of binding sites in the immature central nervous system. In rat cerebral cortex, the receptors are present in the intermediate zone and in association with cells migrating through the cortical plate. Somatostatin receptors in the intermediate zone of fetuses and in the cortical plate of postnatal rats exhibit high and low affinities respectively for the somatostatin analogue MK 678. In the rat cerebellum, the external granule cell layer, a germinal matrix containing interneuron precursors, contains a high density of receptors. These receptors exhibit high affinity for MK 678 throughout the period of cell multiplication. In granule cell cultures from eight-day-old rats, MK 678, octreotide and somatostatin are able to inhibit cAMP formation induced by forskolin or pituitary adenylyl cyclase-activating polypeptide. Somatostatin reduces the intracellular Ca2+ concentration in cultured granule cells; this response desensitizes rapidly. These results suggest that the somatostatin receptors in the external granule cell layer are type 2 receptors (sstr2). A low density of receptors with low affinity for MK 678 was also detected in the external granule cell layer and in the granule cell layer of neonatal rats. In adult rats the cerebellum is devoid of somatostatin receptors. These observations indicate that somatostatin probably exerts morphogenetic activities through different receptor types in several structures of the central nervous system.