Marked decreases in ionized magnesium levels occur during large volume leukapheresis, however, the role of magnesium supplementation has not been carefully studied in this setting. We performed a randomized, double-blind trial of intravenous magnesium sulfate administration in healthy allogeneic subjects undergoing peripheral blood progenitor cell (PBPC) donation. Thirty donors undergoing PBPC collection using standard citrate anticoagulant (ACD-A) and intravenous calcium prophylaxis were randomized to receive either intravenous magnesium (0.2 mg magnesium per mL ACD-A) or placebo during the apheresis procedure. Seventy-five PBPC procedures were evaluated in these 30 subjects, 38 using placebo and 37 using magnesium sulfate. Group characteristics were the same for gender (8 men and 7 women per group), weight (78 vs 81 kg), citrate infusion rate (1.36 vs 1.37 mg/kg/min), and volume processed (16 vs 17 liters). Serum ionized magnesium levels remained within the normal range with use of intravenous magnesium supplementation, but decreased to 39 ?b11% below baseline with use of the placebo solution (p < 0.0001). Serum magnesium levels also decreased significantly following consecutive leukapheresis procedures in the placebo, but not the magnesium-treated donors. Subjects receiving magnesium showed significantly more vigorous parathyroid hormone responses and higher glucose levels, and also tended to have higher serum potassium and ionized calcium levels than subjects receiving placebo. Mild paresthesias, coldness, and nausea occurred in 28%, 20%, and 7% of donors, respectively, with no significant differences between groups. Severe citrate-related symptoms (chest tightness) occurred in only one subject during the study, a donor receiving placebo infusions. We conclude that intravenous magnesium supplementation exerts a significant impact on serum magnesium levels and other metabolic parameters during large volume leukapheresis. Adverse clinical effects were rare in the presence of calcium prophylaxis. A much larger study would be required detect small differences attributable to magnesium infusions. Based on this study, the DTM is re-evaluating guidelines for the use of magnesium supplementation during PBPC donation.