Fetal alcohol syndrome occurs in less than 10% of women who drink heavily during pregnancy. One potential mechanism for this intersubject variation is differences in placental alcohol metabolism. Alcohol dehydrogenase is present at low concentrations in the placenta and is not inducible. CYP2E1 has not been found in human placentas at early gestation time points or in random term placentas. Hepatic CYP2E1 is induced by alcohol and other environmental agents, but induction varies among heavy drinkers and may be genetically controlled. To test whether CYP2E1 is induced in placenta by heavy drinking during pregnancy, we performed a Western blot analysis on placental microsomes from women (n = 8) whose periconceptional average daily absolute alcohol intake was greater than 1 ounce. Using anti-human CYP2E1, bands consistent with CYP2E1 were identified in six samples, although considerable variation among individuals was observed. Among drinking mothers, offspring head size was smaller among those with placental CYP2E1 (p = 0.04). The association between the presence of the protein and smaller birth weight and birth length was equivocal (p = 0.09). Our data are consistent with placental CYP2E1 being inducible by drinking, but with induction being variable among heavy drinking women. We speculate intersubject variation in induction may have a genetic basis and may play a role in susceptibility to alcohol related defects.