To study the acute and long-term effect of GH on its down-stream axis, we measured serum GH-binding protein (GHBP) by ligand-mediated immunofunctional assay. Diurnal changes in serum GHBP were determined by every 20-min sampling for 24 h in four normal short children. There were small or negligible fluctuations in serum GHBP levels, and no correlation with GH pulses was observed. The short-term effect of GH on GHBP levels was assessed in eight GH-deficient children by daily administration of GH (0.1 U/kg) for 10 days. Serum GHBP levels did not significantly change, but IGF-I levels increased significantly. We also studied the long-term effect of GH administration on GHBP levels in seventeen patients with GH deficiency over six months. In twelve out of 17 patients, serum GHBP levels showed an increase when compared to the levels before treatment. In these patients, BMI was not largely changed during treatment, while it tended to decrease in patients whose GHBP levels did not increase. In conclusion, endogenous pulsatile GH secretion and short-term exogenous GH administration had no effect on serum GHBP levels. On the other hand, long-term GH administration increased GHBP levels in 70% of patients with GH deficiency. Changes in BMI may partly be attributed to this change. The direct long-term regulatory effect of GH on GHBP should be further studied.