Observations of normal persons indicated that there was a net shift of serum calcium from the ionized and protein-bound fractions to the anion-bound fraction when these persons received citrate during donor plasmapheresis. To confirm these findings and to extend them to diseased persons, we measured total, ionized, and ultrafilterable Ca concentrations in 11 patients who were undergoing therapeutic plasmapheresis. Anticoagulation was achieved with anticoagulant citrate dextrose solution. Mean concentrations of total, ionized, and protein-bound Ca decreased, whereas the ultrafilterable and anion-bound fractions increased. Our results suggest that protein-bound Ca may be relatively labile and may help to maintain constant levels of ionized Ca. Also, the observed increase in the anion-bound Ca level with citrate infusion suggests a shift from the protein-bound and ionized Ca fractions to this pool.