Large volume leukapheresis (LVL) is increasingly used to collect peripheral blood stem cells (PBSCs) and other mononuclear cells (MNC) for hematopoietic and immune reconstitution, with recent emphasis on increased processing volumes. Decreases in divalent cation levels caused by administration of citrate anticoagulant during LVL can be associated with severe donor reactions, and may limit the rate at which blood can be processed. Several donors at NIH experienced citrate-related hypocalcemic tetany during LVL, in response to which we developed standard operating procedures for the routine administration of prophylactic intravenous calcium solutions during longer apheresis procedures. Other centers have utilized heparin to reduce the amount of citrate returned to the donor, however, this exposes the donor to systemic anticoagulation and may be associated with hematomas or clumping of the apheresis product.