This study assessed the extent to which exposure to maternal smoking during pregnancy was associated with increased risks of psychiatric symptoms in late adolescence (adolescents aged 16-18 years) when due allowance was made for confounding or selection factors associated with maternal smoking during pregnancy. Data were gathered during an 18-year longitudinal study of a birth cohort of 1265 children born in New Zealand. The measures collected included (1) maternal smoking during pregnancy; (2) assessments of psychiatric problems (conduct disorder, major depression, and anxiety and substance use disorders) at age 16 to 18 years; and (3) measures of potentially confounding social, family, and parental factors. Children exposed to maternal smoking during pregnancy had higher psychiatric symptom rates for conduct disorder, alcohol abuse, substance abuse, and depression. Those children whose mothers smoked at least 1 pack of cigarettes per day during their pregnancy had symptom rates that were between 1.4 and 2.5 (median, 2.0) times higher than the children of nonsmokers. Smoking during pregnancy was also associated with a series of adverse or disadvantageous factors that included (1) socioeconomic disadvantage, (2) impaired child-rearing behaviors, and (3) parental and family problems. After adjustment for these confounding and selection factors, smoking during pregnancy was significantly associated with an increased rate of conduct disorder symptoms in late adolescence (P<.001). This effect was more pronounced for male than female adolescents. This study suggests that maternal smoking during pregnancy may contribute to childrens' risk of later externalizing problems. There is a need to further explore the moderating effect of the sex of the child and to clarify the underlying pathophysiological features of this relationship.