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 2 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 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 'ACT 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 GHBPIreceptor in man. The time course of the GH effect appears to be progressive and variable. (Pediatr Res 37: 731-735,1995) Abbreviations GH, growth hormone GHBP, growth hormone-binding protein BMI, body mass index Identification of the serum GHBP and demonstration that the amino acid sequence of GHBP is identical to that of the extracellular domain of the membrane GH receptor have provided new tools to study GH action in man (1, 2). In clinical research, measurement of serum GHBP is the only approach to estimate the GH receptor because there are no accessible cells in which GH receptors can be measured. In man, GHBP probably results from proteolytic cleavage of the membrane receptor as no specific mRNA for the short form of the GH receptor is detected in human tissues (3). The plasma GHBP level is believed to reflect the concentration of tissue GH receptors. In animal models, GH receptors have been shown to be modified in several pathologic situations (4). As membrane GH receptors are regulated by many factors, the level of plasma GHBP is expected to be under a multifactorial control.Among many factors, GH has been shown to play an important role in the regulation of its receptors. However, a controversy has recently arisen concerning the effect of GH on