CBA, C3H, and C57 female mice maintained on a diet of 20 percent ethanol-derived calories prior to and throughout gestation were mated in a diallele cross. Prenatal death, malformations, and fetal weights were directly related to maternal blood alcohol levels, indicating a maternal effect. Fetal abnormalities and maternal blood alcohol levels varied with maternal strain (CBA > C3H > C57) and were inversely related to maternal alcohol dehydrogenase activity. Microsomal ethanol oxidizing systems induction was directly associated with increased fetal abnormalities, being greatest in CBA females. These results indicate that liability for the pattern of malformation observed in this syndrome is dependent on maternal blood alcohol levels, which are determined by the rate of maternal alcohol metabolism as well as the amount of maternal alcohol consumption.