Traditionally, in infants, a serum calcium value less than 7.0 mg/dL is considered to impair cardiac function. In very-low-birth-weight infants, we studied the hypotheses that decline in serum calcium to 6.0 mg/dL (1) would not impair cardiac function and (2) ionized calcium would remain greater than 3.0 mg/dL. We also evaluated the effect of calcium infusion on cardiac function. We studied 15 normokalemic and normonatremic infants whose birth weights were 822 to 1,450 g and were less than 32 weeks' gestation. When serum calcium declined to less than 6.0 mg/dL, 18 mg/kg of calcium as 5% calcium gluconate was infused for 10 minutes. Serum total calcium concentration, blood ionized calcium concentration, ECG, and M-mode echocardiogram were obtained on entry into the study, when the infants were hypocalcemic, immediately after treatment with calcium, and eight hours after treatment. Ionized calcium values were calculated based on serum total calcium and serum protein, and corrected calcium values were calculated based on serum total calcium, serum albumin, and blood pH. In all infants, serum calcium value declined to less than 7.0 and in eight infants to less than 6.0 mg/dL. Assessment of heart rate, systolic blood pressure, ejection fraction, left ventricular systolic time interval, right ventricular systolic time interval, fiber shortening index, and left ventricular mean velocity of circumferential fiber shortening showed no significant alteration from baseline during hypocalcemia or in association with intravenous slow bolus infusion of 18 mg/kg of calcium. In association with a decline in serum total calcium to as low as 6.0 mg/dL, whole blood ionized calcium was maintained at more than 3.0 mg/dL. Serum total calcium and calculated ionized calcium values correlated significantly with measured blood ionized calcium concentrations; however, these measures were not reliable predictors of blood ionized calcium. We speculate that the hypoproteinemia and hypoalbuminemia noted in these infants may result in relative protection of the blood ionized calcium in these infants. We suggest that in neonates with wide ranges in gestation, serum protein, and blood pH levels, total serum calcium and calculated ionized calcium values may be poor measures of derangement of calcium metabolism. Decline in total serum calcium concentration to 6.0 mg/dL was not associated with impaired cardiac function, and slow bolus calcium infusion in these hypocalcemic very-low-birth-weight infants neither improved nor impaired cardiac function.