The in vitro oxidation of 7-ethoxyresorufin was studied in placental microsomes from 47 full-term pregnancies. Placental activities were compared in four groups formed on the basis of maternal smoking history as follows: nonsmokers (n = 12), passive smokers (n = 16), 1 to 20 cigarettes/day (n = 13), and 20+ cigarettes/day (n = 5). Passive smoking was defined as living with someone who smoke cigarettes. Umbilical cord plasma thiocyanate concentrations were measured to confirm histories and were higher when mothers smoked (80 +/- 10 micro M, 1 to 20 cigarettes/day, 116 +/- 8 micro M, 20+ cigarettes/day) than when mothers did not smoke (34 +/- 3 micro M, nonsmokers; 35 +/- 3 micro M, passive smokers). 7-Ethoxyresorufin O-deethylase activity was increased 10- to 30-fold in placentas from smokers. Activity toward 7-ethoxyresorufin in placentas from smokers was markedly inhibited in vitro by addition of 7,8-benzoflavone. Among nonsmokers, percent inhibition of O-deethylase activity by 7,8-benzoflavone was greater (P less than 0.05) in placentas from women passively exposed to cigarette smoke. Human placental monooxygenase activity is sensitive to both active and passive cigarette smoke exposure.