Phenytoin (PHT) is teratogenic in A/J but not in C57BL/6J mice. Teratogenesis in F1 hybrid offspring of these two strains is dependent on the susceptibility of the maternal parent. Hepatic microsomes from untreated pregnant A/J females produced more of both the phenolic and diol metabolites than did microsomes from pregnant C57BL/6J females. This difference disappeared when the animals were pretreated with phenobarbital or phenytoin. It seems unlikely that the genetic difference in susceptibility to PHT-induced teratogenesis can be explained on the basis of maternal metabolism of the drug.