Total bilirubin-binding capacity was measured by Sephadex G-25 gel filtration in 43 clinically well and 45 clinically ill newborn infants between 26 and 41 weeks' gestation. In the well patients, bilirubin-binding capacity, serum albumin concentration, and the molar-binding ratio of bilirubin to albumin were directly related to gestational age. In the sick patients, serum bilirubin-binding capacity and albumin concentration also correlated with gestational age; however, from 32 to 41 weeks' gestation, the mean values for the sick infants were significantly lower than for the well infants. In the sick infants, the molar binding ratio of bilirubin to albumin was also lower than in the well patients and did not correlate with gestational age. The data are in agreement with previous clinical findings indicating an increased risk for low-bilirubin kernicterus among immature infants and suggest that some critically ill term infants may be at risk for kernicterus at serum bilirubin levels below 20 mg/100 ml.