The role of Gilbert's syndrome (GS) in neonatal hyperbilirubinemia, characterized by bilirubin levels higher than 223 microMol/L during the first seven days of life, has been investigated, evaluating the frequency of GS genotype (A(TA)7TAA polymorphism in the promoter of the gene encoding UGT1). The frequency of GS was significantly higher in the hyperbilirubinemic group, even though neither the peak of bilirubin, nor the day on which the highest value was found, differed according to genotype. The normalization of bilirubin levels was slower in neonates with GS. These results confirm the idea that GS is one of the factors contributing to neonatal hyperbilirubinemia, but that other factors play a role in determining neonatal jaundice. The slower decrease of bilirubin levels in A(TA)7TAA homozygous neonates confirms that GS is an important factor in determining a prolonged neonatal jaundice.