Insulin-like growth factor I (IGF-I) is a monomeric peptide with significant homology to proinsulin. IGF-I has a number of potent effects on cultured neural tissue, including the stimulation of mitosis in sympathetic neuroblasts; the promotion of neurite outgrowth in cortical, sensory, and sympathetic neurons; and the induction of oligodendrocyte differentiation. In order to determine the sites in which IGF-I may play a role in neural development in vivo, the pattern of IGF-I gene expression in the developing rat brain has been analyzed by means of in situ hybridization histochemistry. Transient IGF-I gene expression is seen during the maturation of specific groups of functionally related sensory and cerebellar projection neurons. IGF-I mRNA is abundant within developing cerebellar Purkinje cells and in the major cerebellar relay centers, including the inferior olive, medial vestibular and lateral reticular nuclei of the brainstem, and the deep cerebellar and red nuclei. Similarly, IGF-I mRNA is localized in the synaptic stations of the developing olfactory, auditory, visual, and somatosensory systems. For example, in the auditory system, IGF-I mRNA is abundant in the cochlear nucleus, superior olive, lateral lemniscus, medial geniculate body, and inferior colliculus. In each system, IGF-I gene expression is found predominantly in long-axon projection neurons, appearing during a relatively late stage in their development, at a time of maturation of dendrites and synapse formation. The specific timing and selective localization of neuronal IGF-I gene expression described in this study suggest that IGF-I may have a role in the shaping of system-specific synaptic connections or myelinization.