Common diuretics induce hypermagnesiuria which may lead to somatic magnesium depletion and subsequently to serious cardiac arrhythmias. The objectives of the present study were to determine if low doses of the diuretic xipamide cause hypermagnesiuria and to describe the time course of urinary Mg2+ excretion after xipamide in normal probands. Experiments were carried out on 13 healthy adult volunteers given monodoses of placebo, 5, 10 and 20 mg xipamide on separate days in random order. Urine collected at 3, 6, 12 and 24 h after dosing was analyzed for Mg2+ and other solutes. All doses of xipamide induced significant increases of 24-h urinary volume, and C1-, Na+, K+ and Mg2+ excretion when compared to the placebo. Urinary Mg2+ flow was delayed with respect to Na+ flow for all doses of xipamide. Xipamide administered acutely at low doses to healthy subjects causes hypermagnesiuria. The likelihood exists that this substance may induce somatic magnesium depletion when chronically administered, even at low doses.