Hydrochlorothiazide (HTZ) therapy reduces the urinary excretion of calcium (UCa V) in patients with idiopathic hypercalciuria (IH). To test the role of parathyroid hormone (PTH), namely the possibility that HTZ sensitizes the kidney to PTH as the sole or contributory cause of decreased UCa V associated with HTZ therapy, we measured urinary excretion of calcium (UCa V) and cAMP (UcAMP V), the tubular reabsorption of phosphate (TRP), plasma immunoreactive PTH, and the renal response to infused PTH (change in UcAMP V and TRP) in 10 patients with IH. Patients were studied before (control) and after 4 weeks of treatment with HTZ (100 mg/day). HTZ therapy significantly reduced UCa V (mean change, -122 +/- 19 mg/24 h). The UcAMP V, TRP, and plasma levels of calcium, phosphorus, and immunoreactive PTH were initially within the normal range and did not change significantly during HTZ therapy. PTH infusion resulted in a significant increase in the UcAMP V and a significant decrease in TRP during both control and HTZ therapy studies. There was, however, no significant difference in the degree of these renal responses to PTH infusion during the control vs. HTZ therapy studies. We conclude that the hypocalciuric effect of HTZ in patients with IH is independent of changes in PTH secretion, and that HTZ does not cause general sensitization of the nephron, namely proximal tubules, to PTH, as assessed by an increase in UcAMP V and a decrease in TRP.