OBJECTIVE To define normal levels of glucose-6-phosphate dehydrogenase (G6PD) activity in a population of North American white newborns. METHODS We studied 2 white newborn populations, ≥35 weeks of gestation. In the retrospective study, G6PD activity was measured (on clinical indication) in 242 newborns aged ≤7 days. In the prospective study, we measured G6PD activity in umbilical cord blood samples in 347 newborns and daily transcutaneous bilirubin levels in these infants. RESULTS The mean G6PD activity level was 12.3 ± 3.1 units per gram hemoglobin (U/gHb) in the retrospective population and 13.3 ± 1.8 U/gHb in the prospective population, and there was no difference between males and females. The distribution of values suggested that infants with activity levels <7 U/gHb should be considered deficient and 8 infants (6 males and 2 females), all in the retrospective population had such levels. CONCLUSIONS As in other ethnic populations, the mean G6PD activity in white newborn infants is substantially greater than that of white adults. The lower limits of normal are also similar to those of other newborn ethnic groups and of adults. The diagnosis of G6PD deficiency should be considered in any white infant whose G6PD activity is <7 U/gHb.