To determine whether chronic overconsumption of protein might increase renal mass and cause up-regulation of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D] production, 57 male recurrent idiopathic calcium stone formers (RCSF), 29 with hypercalciuria (HCSF; urinary calcium x V, > 7.50 mmol/day) and 28 with normocalciuria (NCSF), were compared with 15 healthy male controls (C) while consuming a free choice diet. Renal mass in RCSF was measured by the sum of the surface areas of right and left kidneys (square centimeters) on plain films of the abdomen by a computer-assisted sonic stylus; in C, renal mass was assessed sonographically. Serum intact PTH and 1,25-(OH)2D were measured radioimmunometrically. In HCSF, urinary phosphate x V (35.9 +/- 1.2 mmol/day) was higher than that in NCSF (29.3 +/- 1.3 mmol/day; P = 0.0009) or C (28.7 +/- 1.8 mmol/day; P = 0.005); urinary creatinine x V (16.5 +/- 0.5 mmol/day) was also higher in HCSF than in NCSF (15.0 +/- 0.5 mmol/day; P = 0.024) or C (13.8 +/- 0.6 mmol/day; P = 0.002). For identical blood levels of ionized calcium and phosphate, the 1,25-(OH)2D/PTH concentration ratio (an index of regulation of 1,25-(OH)2D production) was higher in HCSF (6.5 +/- 1.0) than in NCSF (4.0 +/- 0.3; P = 0.005). In addition, the sum of the surface areas of right and left kidneys was increased in HCSF (163.4 +/- 2.9 cm2) compared with that in NCSF (140.5 +/- 3.1 cm2; P = 0.0001), and it positively correlated with urinary phosphate x V (r = 0.429; P = 0.001) as well as with urinary creatinine x V (r = 0.294; P = 0.026); no such correlation was noted in C. Calcitriol levels were positively related to renal mass in RCSF (r = 0.316; P = 0.018), but not in C. Finally, urinary calcium x V positively correlated with the serum calcitriol/PTH concentration ratio only in RCSF (r = 0.388; P = 0.003). These findings suggest that protein overconsumption may cause an increase in renal mass and up-regulate calcitriol production in some male RCSF, an effect that would subsequently cause "idiopathic" hypercalciuria.