Idiopathic hypercalciuria (IH) is the most common cause of calcium oxalate nephrolithiasis. Increased intestinal calcium absorption and bone resorption and decreased tubule calcium reabsorption may be caused by elevated serum 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] in some patients but not in those with normal serum 1,25(OH)(2)D(3) levels. Because 1,25(OH)(2)D(3) exerts its biological actions through binding to the cellular vitamin D receptor (VDR), the present study was undertaken to test the hypothesis that VDR levels are elevated in IH patients. Ten male IH calcium oxalate stone-formers were paired with controls matched in age within 5 yr and lacking a history of stones or family history of stones. Blood was obtained for serum, peripheral blood monocytes (PBMs) were separated from lymphocytes and other mononuclear cells, and PBM VDR content was measured by Western blotting. The PBM VDR level was 2-fold greater in IH men at 49 +/- 21 vs. 20 +/- 15 fmol/mg protein, mean +/- sd; P < 0.008. Serum 1,25(OH)(2)D(3) levels were not higher than controls (48 +/- 14 vs. 39 +/- 11 pg/ml; P < 0.068). In conclusion, PBM VDR levels are elevated in IH calcium oxalate stone-formers. The elevation could not be ascribed to increased serum 1,25(OH)(2)D(3) levels. These results suggest that the molecular basis for IH involves a pathological elevation of tissue VDR level, which may elevate intestinal calcium absorption and bone resorption and decrease renal tubule calcium reabsorption. The mechanism for increased VDR in IH patients with normal serum 1,25(OH)(2)D(3) levels is unknown.