The short- and long-term effects of hGH treatment on growth hormone (GH)-binding protein (GHBP) were examined in 18 prepubertal children, aged 1.5-10 y, with isolated idiopathic GH deficiency. The patients were studied before and at regular intervals during 24 mo of hGH therapy (0.6 IU/kg/wk, given daily). Pretreatment GHBP values were low: 14.6 +/- 1.2% of radioactivity (p < 0.0001 versus normal prepubertal children). After the first hGH injection, GHBP levels fell significantly at 6 h (8.2 +/- 1.3% of radioactivity) and then remained at basal level during the first week. Under hGH therapy, an increase in GHBP was observed, but it occurred at different times of treatment, from 1 to 12 mo, and the mean GHBP value became significantly higher than the value before treatment after 12 mo of therapy. An increase in serum IGF-I level was observed as soon as 1 wk of hGH therapy, and after 3 mo, the mean IGF-I value was normal. No correlation was found between the increase in GHBP, IGF-I levels, and the growth velocity at 12 and 24 mo of treatment. These findings support the role of GH in the regulation of GHBP/receptor in man. The time course of the GH effect appears to be progressive and variable.