Extract: Infants of two groups, one of 16, one of 14 infants, who weighed < 1.3 kg at birth (mean 1.01 ± 0.05 kg), were studied from age 14 days until they reached 1.8 kg body weight. Infants were pair-matched for gestational age and birth weight and one member was randomly allocated to two treatment groups. Infants in group A received no calcium supplement and those in group B received calcium lactate, 800 mg/kg/24 hr, in divided doses with each feed. All were fed “Improved” SMA, 200 ml/kg/24 hr, 160 cal/kg/24 hr, and were given a multivitamin preparation containing 500 IU vitamin D2/dose. The infants' weekly length gain did not differ between groups (1.08 ± 0.04 cm/week vs 1.11 ± 0.04 cm/week; mean ± SEM). Mean weight and head cercumference increments also were similar (group A, 163 ± 6 g/week; 1.12 ±0.03 cm/week; group B, 170 ± 6 g/week and 1.18 ± 0.03 cm/week). An increase in blood pH from 7.33 ± 0.01 to 7.41 ± 0.01 (P < 0.01) in group A babies was associated with a decrease in PCO2 from 44.2 ± 1.0 to 38.9 ± 1.4 mm Hg. Values remained unchanged with age in group B babies. After institution of calcium supplementation, base excess values differed transiently between groups (at age 5 weeks, group A −0.16 ± 0.56 mEq/liter, group B −1.17, ± 0.76 mEq/liter; P < 0.05). Mean ionic calcium values remained unchanged in group A (2.37 ± 0.06 mEq/liter), but increased slightly from 2.42 ± 0.06 to 2.57 ±0.04 mEq/liter in group B (P < 0.05).Total plasma calcium differed transiently between groups after calcium supplementation had started in group B (Group A, 4.53 ± 0.08 mEq/liter; group B, 4.82 ± 0.12 mEq/liter; P < 0.05), and plasma Mg and P levels were lower in group B babies than in group A babies (P < 0.01). All infants remained somewhat hypoproteinemic throughout the study; mean values of plasma total protein averaged 4.5 g/100 ml. Mean urinary excretion rates of calcium initially were 0.17 mEq/kg/24 hr in group A babies and 0.18 mEq/kg/24 hr in group B infants, and no increase was seen with calcium supplementation. Fecal excretion of calcium (percentage of intake) decreased from 70% to 33% in group B babies after calcium supplementation. Calcium retention rates (mEq/kg/24 hr) were similar in both groups initially but increased subsequently in group B from 1.20 to 7.33 mEq/kg/24 hr and were 3 times as high in group B than in group A during the second and third balances. Urinary phosphorus excretion was initially similar in both groups (group A, ISA ± 2.2 mg/kg/24 hr; group B, 32.4 ± 5.5 mg/kg/24 hr), but decreased to half this value in infants of group B after calcium supplementation had started (P < 0.02). Group B infants showed a higher percentage fecal fat excretion than group A infants during the second and third balance. In 9 of 10 paired radiographs of the knee and tibia group B infants showed better defined bone texture and/or wider cortices than did group A infants. We suggest that prevention of the “bone disease of very low birth weight (VLBW) infants” may be accomplished by suitable calcium supplements. Speculation: As a consequence of their special requirements and the unavailability of appropriately constituted infant formulas, infants born very prematurely fail to achieve intrauterine accretion rates for many minerals. Postnatal growth may also be jeopardized. We believe that for optimal postnatal growth infants born very prematurely require sufficient nutrients to parallel intrauterine accretion rates.