Fetal alcohol syndrome occurs in < 10% of women who drink heavily during pregnancy. One mechanism for this intersubject variation may be differences in placental alcohol metabolism. Alcohol dehydrogenase (ADH), present in small amounts in placenta, is not inducible. CYP2E1 has not been found in early human placentas or random term placentas. Hepatic CYP2E1 is induced by alcohol, 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 western blots on placental microsomes from women (N=10) whose periconceptual average daily absolute alcohol intake was greater than 1 ounce (more than 14 drinks per week). In 4 samples, faint bands consistent with CYP2E1 were identified using anti-human hepatic CYP2E1. To confirm these findings, microsomal metabolism studies were performed using a placenta with a positive western blot, an NADPH-generating system and the CYP2E1 specific substrate, chlorzoxazone (range: 50-500 μM). For each substrate concentration, multiple timed reactions were incubated, and the formation of the CYP2E1 product, 6-hydroxychlorzoxazone, was measured using HPLC. The initial velocity for each substrate concentration was determined from the slope of the linear portion of the product formation-time curve. From the Michaelis-Menten relationship, the resulting Km was about 200 μM, which is similar to that of hepatic CYP2E1. From these data, we conclude placental CYP2E1 is induced by heavy drinking, but induction varies among heavily drinking womEn. We speculate intersubject variation in induction may have a genetic basis and may play a role in susceptibility to alcohol related birth defects.