Little attention has been paid to interactions between circulating levels of calcium, PTH, and 1,25-dihydroxycholecalciferol [1,25(OH)2D] and bone mineral density in primary renal magnesium deficiency. Plasma and urinary electrolytes, and circulating levels of calciotropic hormones were studied in 13 untreated patients with primary renal tubular hypokalemic alkalosis with hypocalciuria and magnesium deficiency. The blood ionized calcium concentration was significantly lower in patients than in controls. Despite this fact, PTH and 1,25-(OH)2D levels were similar in both groups of subjects. The negative linear relationships between PTH and ionized calcium, which significantly differed between Gitelman patients and healthy subjects in terms of intercept; the negative relationship between ionized calcium and 1,25-(OH)2D, which was comparable in both groups; and the positive relationship between 1,25-(OH)2D and PTH, which was identical in both groups, point both to a blunted secretion of PTH induced by magnesium depletion and to the lack of interference of the latter with the activation of 1 alpha-hydroxylase by PTH. The similar bone mineral density at the lumbar spine by dual energy x-ray absorptiometry in 11 patients and 11 healthy subjects argues against chronically sustained negative calcium balance.