In order to gain further insight into the mechanisms of calcium (Ca) homeostasis in hypercalciuria, we studied 32 lithiasic patients who were divided into three groups: normocalciuric patients (NC; n = 11), patients with absorptive hypercalciuria (AH; n = 12) and patients with renal hypercalciuria (RH; n = 9). The patients were investigated on 3 occasions: during a random diet, after a Ca-restricted diet and during a Ca tolerance test. The following determinations were made: Ca intake, Ca tubular reabsorption (Ca TR), plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) levels, natriuresis and urinary protein-bound Gla. The latter was measured as a marker of urinary nephrocalcin excretion. Ca TR was decreased in hypercalciuric patients (HC). AH but not RH patients normalized their Ca TR during fasting. Plasma PTH and 1,25(OH)2D levels were similar in all the groups on the 3 occasions. Natriuresis was elevated in RH during the fasting period (p < 0.02 vs. AH). Compared with NC, protein-bound Gla urinary excretion rates (UER) were enhanced in AH after the Ca-restricted period (p < 0.02) and in RH during fasting (p < 0.02). In AH, a strong positive correlation was found between Ca TR and protein-bound Gla UER (r = 0.79, p = 0.002) following a Ca-restricted diet. In the HC group as a whole, fasting protein-bound Gla UER were correlated to plasma 1,25(OH)2D levels (r = 0.68, p < 0.001). In conclusion, the results suggest that PTH directly or indirectly through 1,25(OH)2D increases nephrocalcin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)