The exogenous administration of bovine parathyroid hormone or parathyroid extract has been used to differentiate states of parathyroid hormone resistance and parathyroid gland secretory failure, and in recent years to test renal 1,25-dihydroxyvitamin D (1,25-(OH)2-D) secretion. We evaluated the effect of synthetic human parathyroid hormone (hPTH-(1-34] administration on the renal 1,25-(OH)2-D, phosphaturic and cyclic-AMP responses in eleven normal young adults. The intravenous administration of 200 units of hPTH-(1-34) over 10 min produced a 1.3-5.4 fold increase (P less than 0.01) in renal phosphate clearance and a 19-75 fold increase (P less than 0.0001) in urinary cyclic-AMP excretion. Serum 1,25-(OH)2-D levels showed a small and insignificant change at 2.5 h and a significant (P less than 0.05) but small (21 +/- 24 pmol/l) increase at 7 h after the first injection. In eight subjects a second injection of hPTH-(1-34) was given at 7 h. In these individuals serum 1,25-(OH)2-D levels at 24 h were 40 +/- 14 pmol/l (44%) higher than baseline (P less than 0.01), but were variable over the 24 h period. The present study shows that hPTH-(1-34) produces renal phosphaturic and cyclic-AMP responses in normals similar to those produced by bovine PTH preparations. However, the serum 1,25-(OH)2-D response to one or two intravenous injections of hPTH-(1-34) is small, variable, and inconsistent and, therefore, will not provide a consistent way of stimulating renal 1,25-(OH)2-D secretion.