The administration of oral calcium (Ca) supplements (Tums ?) to plateletpheresis donors is widely practiced to counteract symptoms associated with acute decreases in serum ionized calcium (iCa) concentration due to infusion of citrate anticoagulant. However, the clinical usefulness of this practice has not been evaluated. We studied the associations of donor symptoms and various laboratory parameters in a randomized placebo controlled study of oral Ca carbonate administration. Twenty-three donors (12 males and 11 females) underwent 4 plateletpheresis procedures each, receiving in random order, elemental Ca (1 or 2 g orally), or a corresponding placebo, 30 minutes prior to the procedure. Ten of these donors underwent a fifth procedure with a 4g Ca supplementation. All procedures were performed at fixed citrate infusion rates of 1.5 mg/kg/min. Oral Ca induced dose-sensitive changes in parathyroid hormone (iPTH), total calcium (tCa), and iCa. Compared to placebo, the most marked overall attenuation in iPTH release and the most rapid early improvement in tCa and iCa concentratons occurred after the 1g Ca dose. These effects were smallest after the 4g Ca dose. The serum tCa and iCa concentrations one day after the procedure were higher, and iPTH were lower, in the Ca supplemented group. The urine excretion of Ca and Mg was increased at the end of procedure, was not affected by Ca dose, and returned to baseline within 24 hours of the procedure. Plateletpheresis also induced significant changes in serum alkaline phosphatase, 1,25-dihydroxyvitamin D, and osteocalcin. The severity of donor symptoms during apheresis was associated with the extent of decrease in serum iCa and ionized magnesium (iMg) concentrations, and also with albumin, creatinine and vitamin D concentrations. Females experienced more symptoms than males. However, the association of gender with symptoms was not significant after adjustment for lower serum albumin, creatinine and tMg in the females. Compared with placebo, ingestion of 2g Ca resulted in reduced paresthesias. However, in general, ingestion of Ca did not significantly improve the overall symptom scores. Thus, oral Ca supplementation administered prior to the apheresis procedure resulted in modest improvements in donor symptoms and in critical serum analytes.