Animal studies have shown that GH is necessary for the increased renal production of calcitriol during dietary phosphorus deprivation (PD). These studies suggest that this adaptive change in vitamin D metabolism is mediated through insulin-like growth factor-I (IGF-I) and/or insulin. We subjected 16 GH-deficient children to 96 h of severe dietary PD twice, first before and again during recombinant GH replacement. Half of the children received low dose and half received high dose replacement with recombinant GH. We measured renal tubular reabsorption maximum for phosphate corrected for glomerular filtration rate (TmP/GFR), PTH, IGF-I, calcidiol, and calcitriol pre- and postdietary PD, both off and on GH. We also assessed insulin secretion during an oral glucose load (OGTT) off and on GH. Basal PTH, calcidiol, calcitriol, and fasting blood sugar were unaffected by GH therapy. PD did not affect PTH or calcidiol either off or on GH. Basal TmP/GFR rose on GH therapy (4.8 +/- 0.2 to 6.3 +/- 0.4 mg/dL) and with PD (4.8 +/- 0.2 to 5.7 +/- 0.2 mg/dL off and 6.3 +/- 0.4 to 7.8 +/- 0.3 mg/dL on GH). The increments due to PD and GH therapy were additive. The increments on GH were independent of the GH dose. Before GH replacement, calcitriol did not rise during PD (22.3 +/- 2.1 to 23.3 +/- 1.9 pg/mL), but during GH therapy, PD caused a significant rise in calcitriol (23.8 +/- 2.5 to 33.3 +/- 2.4 pg/mL; P less than 0.0001). The increment in calcitriol during PD was significantly greater in the high dose than it was in the low dose group (11.7 +/- 1.5 vs. 7.2 +/- 1.6 pg/mL; P less than 0.05). GH therapy caused a rise in the IGF-I level that was significantly greater in the high dose (0.26 +/- 0.03 to 3.15 +/- 0.56 U/mL) than in the low dose (0.27 +/- 0.02 to 0.68 +/- 0.13 U/mL) group. Insulin in response to OGTT was significantly greater after GH therapy (4155 +/- 600 microU/mL.min off GH; 6504 +/- 1153 microU/mL.min on GH), although there was no difference between the low and high dose groups. Regression analysis demonstrated a correlation between the change in calcitriol during PD and the IGF-I level (r = 0.83). There was no correlation between insulin levels and the change in calcitriol or between IGF-I or insulin levels and the increment in TmP/GFR during GH therapy.(ABSTRACT TRUNCATED AT 400 WORDS)