The mechanism of hypocalcemia was assessed prospectively in 10 gastroenterological hypomagnesemic patients. Baseline serum magnesium was 0.9 +/- 0.1 mg/dl and calcium, 7.2 +/- 0.4 md/dl. Plasma 25-hydroxyvitamin D (25 (OH)D) was low in 5 patients and normal in the others. Plasma parathormone (PTH) and urinary cyclic AMP (ur. cAMP), although twofold above normal values, were inappropriately low and increased sharply after a magnesium bolus injection. There was no renal resistance to PTH as ur. cAMP increased after i.v. bovine PTH bolus injection. Subsequently, patients were randomly divided into 2 groups, each including patients with low or normal levels of 25 (OH)D, receiving either MgCl2 (group I) or 1 microgram/d of 1-alpha (OH)D (group II) for one week. Although magnesium status remained low in group II patients, increase in plasma calcium was identical in both groups. Serum calcium levels in patients receiving combined 1-alpha (OH)D and MgCl2 during a second week of treatment returned to normal. In the 4 tested patients, plasma 1,25 (OH)2D levels were low before, but also after correction of hypomagnesemia, suggesting that low level of 1,25 (OH)2D might not be due to hypomagnesemia. Therefore, treatment with low dosage of 1-alpha (OH)2D associated with magnesium chloride repletion can be recommended to restore normal calcium homeostasis in patients with intestinal hypomagnesemia.