Glutathione S-transferases (GSTs) are a major group of phase II detoxification enzymes involved in the metabolism of both endogenous and xenobiotic compounds. In addition to their catalytic function in detoxification, GSTs participate in binding to nonsubstrate ligands such as bilirubin. Ligandin, which is one of the principal hepatic-binding proteins, is also a member of the GST family. The aim of the present study was to investigate the possible relationship between neonatal jaundice and the GST gene polymorphisms. The study cohort consisted of a patient group of 116 newborns (plasma bilirubin levels > or = 15 mg/dl) and a control group of 54 newborns (plasma bilirubin levels <13 mg/dl). In the patient group, the null genotype frequencies in GSTM1 and GSTT1 were 52.6 and 19%, respectively; in the control group, these were 63 and 27.8%, respectively. The frequencies of GSTM1 and GSTT1 were similar in the patient and control groups (p > 0.05). Total bilirubin levels were found to be significantly higher in patients with the GSTM1 null genotype than in patients with the GSTM1 wild genotype (p = 0.042). There was no statistically significant difference in total bilirubin levels between patients with the null GSTT1 genotype and those with the wild GSTT1 genotype. It is conceivable that there is a relation between GSTM1 gene polymorphism and total bilirubin levels in neonatal jaundice. We suggest that GSTM1 gene polymorphisms may affect ligandin functions in hepatocytes, which are important in bilirubin transportation. Consequently, patients with the GSTM1 null genotype may have higher total levels of bilirubin.