The mechanisms underlying the effects of recombinant human growth hormone (rhGH) on vitamin D, mineral, and bone metabolism are not known. We examined whether these effects are mediated by parathyroid hormone (PTH) by measuring renal phosphorus (P) and calcium (Ca) handling, serum calcitriol, and markers of bone turnover for 24 h before and 72 h after an infusion of hPTH(1–34) in eight healthy postmenopausal women at baseline and following short-term (1 week) and sustained (5 weeks) rhGH treatment. On short-term rhGH, serum phosphorus and basal TmP/GFR were unaffected, but the fall in TmP/GFR after hPTH infusion was exaggerated (integrated response: −99.2 ± 22.3 versus −144.1 ± 15.0 minute-mg/dl, P = 0.0021). Basal calcitriol levels rose from 115 ± 17 to 163 ± 16 pM (P = 0.0002), but the increase in calcitriol following hPTH infusion was unaffected by short-term rhGH. The basal Ca excretion index (CEI) rose from 0.054 ± 0.005 to 0.073 ± 0.007 mM (P = 0.0095), but markers of bone turnover were unaffected. With sustained rhGH treatment, serum P (1.47 ± 0.05 mM), basal TmP/GFR (4.29 ± 0.24 mg/dl), and basal CEI (0.067 ± 0.005 mM) were elevated compared with control values, and the PTH-induced lowering of TmP/GFR was again enhanced (- 158.7 ± 22.8 minute-mg/dl, P = 0.0021). Basal calcitriol concentrations returned to control levels (108 ± 10 pM), but the calcitriol response to hPTH remained unchanged. Markers of bone remodeling were elevated with sustained rhGH treatment. Neither short-term nor sustained rhGH affected plasma ionized Ca, serum PTH levels, or the magnitude of the acute hydroxyproline, calcitriol, or cAMP responses to hPTH. We conclude that GH has PTH-independent effects on renal phosphate handling and 1α-hydroxylase activity, exerting its effects at a postreceptor step beyond adenylate cyclase activation.