We have measured monooxygenase activities in placentas from 82 women who smoked throughout their pregnancies and correlated these with the presence or absence of major somatic anomalies. Monooxygenase activities toward benzo(a)pyrene and ethoxyresorufin in placentas from 18 abnormal infants were compared with activities in placentas from 64 concurrently studied normal infants. Placentas from normal infants were found to have high levels of monooxygenase activities and low apparent Kms toward ethoxyresorufin (10(-7) M), reflecting induction of cytochrome P-450 enzymes usually associated with maternal cigarette smoking. Placentas from the abnormal infants, however, had significantly lower monooxygenase activities and higher apparent Kms toward ethoxyresorufin (10(-5) M), indicating that induction of specific cytochrome P-450 systems occurred less frequently among placentas from abnormal infants. The reasons for this association are unclear. Apparent lack of induction of monooxygenase activity occurred most frequently in placentas from anencephalic infants but was neither exclusively nor consistently found with this defect. No specific maternal condition or environmental exposure associated with lack of monooxygenase induction was identified.