• The present study evaluated 12 infants with birth weights less than 2000 g who received human milk plus a multivitamin supplement and 20 similar infants who received standard cow's milk formula for 16 weeks from the time of initial hospital discharge. Examination at birth, at hospital discharge (study entry), at 4 and 16 weeks after hospitalization, and at 52 weeks of age revealed no intergroup differences in body weight, length, and head circumference. Hypophosphatemia (plasma phosphorus concentration ≤1.45 mmol/L) developed in 6 infants fed human milk (5 infants at 4 weeks and 1 infant at 16 weeks of study). Mean vitamin D intakes, but not calcium and phosphorus intakes, were significantly lower during hospitalization in human milk–fed infants with hypophosphatemia (44 [25, SD] IU/d) compared with those without hypophosphatemia (322  IU/d). These data indicate that human milk–fed, low-birth-weight infants are at risk for hypophosphatemia following initial hospital discharge. Plasma calcium, phosphorus, and alkaline phosphatase concentrations at hospital discharge may not predict the infants at risk. Vitamin D supplementation early in the infants' hospital course may prevent hypophosphatemia.