Recent data suggest that levels of glutathione S-transferase Alpha 1-1 in umbilical cord plasma may be a good indicator of neonatal hepatocellular integrity. In order to fully understand the significance of this new marker we compared the values of glutathione S-transferase Alpha 1-1 (GSTA1-1) with that of the well known liver function markers alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in arterial and corresponding venous umbilical cord blood of 93 patients. In addition, in 49 of these patients maternal venous blood was also studied. Both arterial and venous umbilical cord GSTA1-1 and AST levels were significantly higher than corresponding maternal venous levels, whereas ALT levels were not. Arterial umbilical cord GSTA1-1 correlated significantly with the corresponding AST and ALT levels (R = 0.46, P < 0.0001 and R = 0.41, P < 0.0001, respectively). Arterial umbilical cord AST correlated significantly with corresponding ALT levels (R = 0.58, P < 0.0001). Arterial umbilical cord plasma GSTA1-1 levels were significantly lower in the cesarean delivery group as compared to the vaginal birth group, whereas no difference was noted for AST or ALT. Arterial umbilical cord AST and GSTA1-1 levels correlated significantly with base deficit (R = 0.29, P = 0.005; R = 0.29, P = 0.005, respectively), whereas ALT did not (R = 0.06, P = 0.54). Arterial umbilical cord AST, ALT, and GSTA1-1 levels correlated significantly with birthweight. In conclusion, GSTA1-1 levels as assessed in neonatal umbilical cord blood, being unrelated to maternal levels, seem to be a more sensitive marker for early neonatal hepatocellular integrity as compared to ALT or AST and even might detect impaired hepatocellular integrity due to the vaginal birth process. Umbilical cord GSTA1-1 may provide a valuable indicator of neonatal condition immediately after birth, the clinical relevance of which needs to be further established.