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PURPOSE: Several studies have suggested an association between maternal smoking during pregnancy and both attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) in the offspring of women who smoke during pregnancy. However, it is unclear whether one or both of the documented links are spurious, given the considerable comorbidity between these disorders. The main aim of this study was to disentangle the association between maternal smoking during pregnancy with psychopathological outcomes, adjusting for possible confounders. METHODS: Two large, identically designed, longitudinal, case-control family studies of male and female probands with and without ADHD were combined. We used data from the nonreferred siblings of the probands from both studies (n = 536). All subjects were blindly assessed with structured diagnostic interviews. Logistic regression analysis was used to determine the adjusted effect of exposure to maternal smoking during pregnancy. RESULTS: Among all siblings, maternal smoking during pregnancy was significantly associated with ADHD, independent of CD and other covariates. In contrast, maternal smoking during pregnancy was a risk factor for CD only in siblings of control probands, after adjusting for covariates. CONCLUSIONS: These results support the hypothesis that maternal smoking during pregnancy is a risk factor for both ADHD and CD, independently of each other. However, the risk for CD appears to be conditional on family risk status. [ABSTRACT FROM AUTHOR]