Fifty-three patients were studied intraoperatively during massive transfusion of CPD-preserved blood and fresh frozen plasma (FFP). Baseline concentrations of total calcium (Ca), ionized calcium (Ca2+), albumin, total protein, and hydrogen ion concentration [H+] were measured prior to transfusion, at intervals during transfusion of 2500 ml of blood, and at the end of transfusion. Systemic arterial pressure (BPI, central venous pressure (CVP) and/or pulmonary artery wedge pressure (PAW), and corrected Q-T intervals on electrocardiographic tracings were measured at the time blood samples were obtained. Ca2+ decreased from 2.07 ± 0.03 mEq/L at baseline to 1.52 ± 0.05 mEq/L (p < 0.01) during transfusion at peak rates of 33 ± 3.2 ml/kg/hr. Following completion of transfusion, Ca2+ was significantly higher than at peak rates of transfusion, but still below baseline. Serum citrate levels rose from a baseline value of 1.87 ± 0.17 mg/dl to 6.30 ± 0.49 mg/dl (p < 0.01) at peak rate of transfusion and fell to 4.76 ± 0.48 immediately upon completion of transfusion (p < 0.011. The changes in Ca2+ and serum citrate levels showed a strong statistical correlation with each other. [H+] increased, but not significantly, at peak rates of infusion; after completion of transfusion, [H+] was significantly lower than during peak rates of transfusion. Ca levels were 4.10 ± 0.05 mEq/L at baseline, 3.90 ± 0.05 mEq/L at peak rates of infusion, and 3.89 ± 0.06 mEq/L after transfusion was completed. Albumin levels at the same sampling intervals were 3.60 ± 0.07, 3.71 ± 0.06, 3.87 ± 0.07 g/dl, respectively. Total protein levels were 5.95 ± 0.07, 5.67 ± 0.07, and 5.88 ± 0.09 g/dl, respectively. Corrected Q-T intervals were significantly prolonged at peak rates of transfusion and upon completion of transfusion. Correlation between changes in Ca2+ and corrected Q-T intervals was statistically significant. However, hemodynamic variables remained stable throughout the period of observation. Massive transfusions depressed Ca2+ due to administration of citrate, but this was only transient. Ca2+ rapidly returned to normal levels as citrate was redistributed and metabolized. The changes in Ca2+ were without hemodynamic significance. Clinically significant metabolic acidosis due to transfusion was not observed. We conclude, therefore, that as long as circulating volume is maintaines, as determined by measurement of CVP or PAW, calcium salts need to be administered during blood replacement, either empirically on the basis of rate or volume or transfusion, or on the basis of changes in samples indicate the development of metabolic acidosis.