Because insulin-dependent diabetes mellitus is associated with altered electrolyte metabolism and a derangement of the parathyroid hormone (PTH)-vitamin D endocrine system, we studied 23 children with diabetes (age 9.4 +/- 2.5 years) and found lower serum values for total and ionized calcium, magnesium, intact PTH, calcitriol, and osteocalcin than in age- and sex-matched control subjects. All patients were given magnesium orally (6 mg/kg daily of elemental magnesium) for up to 60 days. During treatment, serum magnesium, total and ionized calcium, intact PTH, calcitriol, and osteocalcin concentrations significantly increased, reaching control values. After a 3-day low-calcium diet, the patients had a significantly reduced delta-increment of PTH and calcitriol in comparison with values obtained during hypomagnesemia. After magnesium repletion, the delta-increments of both PTH and calcitriol, in response to the low-calcium diet, were not significantly different from control values. These data suggest that magnesium deficiency plays a pivotal role in altering mineral homeostasis in insulin-dependent diabetes mellitus.