Two clinical studies were conducted to determine the effect of different doses of growth hormone (GH) on prepubertal growth in GH-deficient boys. In one study, GH doses of 1.0 and 1.5 IU/kg/week (0.33 and 0.5 mg/kg/week) were given to groups of five children and compared with a conventional Japanese dose of 0.5 IU/kg/week (0.17 mg/kg/week) in 15 children. A significant dose-dependent increase in height velocity occurred in the first year of treatment, but differences between doses were not significant thereafter. In a second study, GH was administered to ten boys at a dose of 0.5 IU/kg/week for the first year, 0.75 IU/kg/week for the second year, 1.0 IU/kg/week for the third year and 0.5 IU/kg/week for the fourth and subsequent years (0.17, 0.25, 0.33 and 0.17 mg/kg/week, respectively). During the second and third years of GH treatment, these boys had significantly higher growth rates than controls, who were given GH at 0.5 IU/kg/week (0.17 mg/kg/week) throughout, indicating successful reduction in 'waning' of the treatment effect. At the end of the fourth year, the different protocols from the two studies had both resulted in a greater height SDS than the controls, and did not advance bone maturation. In conclusion, these protocols may be effective in increasing prepubertal height gain in children with GH deficiency.