Postnatal growth and development are coordinated by genetic and environmental influences and numerous growth factors. The growth hormone-insulin-like growth factor-I (GH-IGF-I) axis plays an essential role in these processes. Although the GH-IGF-I axis is a closely coordinated system, both GH and IGF-I have independent actions, many of which have become apparent more recently following the characterization of clinical syndromes and the development of mouse models. Genetic manipulation of mice has enabled investigators to re-examine many of the established hypotheses regarding the GH-IGF-I axis. Results gleaned from a mouse model created by tissue-specific gene deletion of liver IGF-I has enabled investigators to re-evaluate the original 'somatomedin hypothesis'.