Growth hormone is the major regulator of postnatal growth. Although intrauterine growth seems to be largely growth hormone independent, gene knockout studies have established the pivotal role of the IGF system in both prenatal and postnatal growth. The original "somatomedin hypothesis" postulated that all of the growth-promoting actions of growth hormone were mediated by IGFs. Several in vitro and in vivo studies have suggested, however, that growth hormone may have specific growth-related actions in addition to stimulating IGF production, including promoting differentiation of prechondrocytes at the growth plate and stimulation of synthesis of proteins involved in IGF transport and clearance. An integrated model of interrelated role(s) of growth hormone and IGF in skeletal growth is proposed.