The purpose of this review has been to emphasize, in general terms, the major aspects of the structure, expression, and regulation of the IGF-I and IGF-II genes. The complex organization of these genes provides ample opportunities for control of gene expression at multiple levels. It is important to realize that regulation at one level can influence regulation at a different level. While such regulatory interactions are characteristic of both the IGF-I and IGF-II genes, they are particularly evident in the case of IGF-I gene expression. For example, the choice of transcription start site influences the length and the sequence of the 5'-UTR, which can influence mRNA translatability and prepeptide sequence, which may influence the amounts of protein produced and, potentially, the intracellular processing and secretion of the final gene product, the mature hormone. Another example is provided by the alternative splicing of E-peptide-encoding exons, which determines the primary structure of the prohormone, which could influence its processing, stability, or function. Thus, this complex gene organization may reflect the need to carefully control, through a multilevel process, the synthesis, processing, and secretion of these important regulatory peptides.