To investigate the potential role(s) of the insulin-like growth factors (IGFs) in embryogenesis, we have used in situ hybridization histochemistry to localize mRNAs for IGF-I, IGF-II, and the type I IGF receptor during an early period in rat embryonic development (embryonic days 14 and 15). IGF-I and IGF-II mRNAs were found in distinctly different patterns of cellular distribution. IGF-I mRNA was particularly abundant in undifferentiated mesenchymal tissue in the vicinity of sprouting nerves and spinal ganglia, and in circumscribed regions of the developing face that corresponded to the target zones of the trigeminal nerve. IGF-I mRNA was also found in aggregations of mesenchyme surrounding, but not in developing muscle and cartilage. IGF-I mRNA was selectively concentrated in areas of active tissue remodeling, such as the cardiac outflow tract, and was undetectable in liver, pituitary, and nervous system at this early stage of organogenesis. IGF-II mRNA was abundant in developing muscle, cartilage, and vascular tissue, and in the embryonic liver and pituitary. IGF-II mRNA was also conspicuous in areas of vascular interface with the brain, such as the choroid plexus and the organum vasculosum of the lamina terminalis. Messenger RNA for the type I IGF receptor was widely distributed in embryonic tissues, but the highest level were seen in the ventral floorplate of the hindbrain, where specialized neuroepithelial cells act as guides for axonal targeting. In conclusion, the different cellular patterns of expression of genes for IGF-I and IGF-II indicate that these two IGFs are differently regulated and, thus, may have significantly different roles in the process of embryonic development. Furthermore, the early and widespread expression of the type-I IGF receptor gene, in contrast to the relatively limited and localized pattern of IGF-I gene expression, is consistent with the view that this receptor may mediate the effects of IGF-II as well as IGF-I during embryogenesis.