We measured the serum bilirubin concentrations in 2,416 consecutive infants admitted to our well-baby nursery. The maximum serum bilirubin concentration exceeded 12.9 mg/dL (221 mumol/L) in 147 infants (6.1%), and these infants were compared with 147 randomly selected control infants with maximum serum bilirubin levels less than or equal to 12.9 mg/dL. In 66 infants (44.9%), we identified an apparent cause for the jaundice, but in 81 (55%), no cause was found. Of infants for whom no cause for hyperbilirubinemia was found, 82.7% were breast-fed v 46.9% in the control group (P less than .0001). Breast-feeding was significantly associated with hyperbilirubinemia, even in the first three days of life. The 95th percentile for bottle-fed infants is a serum bilirubin level of 11.4 mg/dL v 14.5 mg/dL for the breast-fed population, and the 97th percentiles are 12.4 and 14.8 mg/dL, respectively. Of the formula-fed infants, 2.24% had serum bilirubin levels greater than 12.9 mg/dL v 8.97% of breast-fed infants (P less than .000001). When compared with previous large studies, the incidence of "readily visible" jaundice (serum bilirubin level greater than 8 mg/dL) appears to be increasing. The dramatic increase in breast-feeding in the United States in the last 25 years may explain this observation. There is a strong association between breast-feeding and jaundice in the healthy newborn infant. Investigations for the cause of hyperbilirubinemia in healthy breast-fed infants may not be indicated unless the serum bilirubin level exceeds approximately 15 mg/dL, whereas in the bottle-fed infant, such investigations may be indicated if the serum bilirubin exceeds approximately 12 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)