We evaluated the role of pregnancy, delivery, and infancy complications (PDICs) in the etiology of attention deficit hyperactivity disorder (ADHD) and addressed issues of comorbidity and familiarity by testing multiple hypotheses. Subjects were 6-17-year-old boys with DSM-III-R ADHD (n = 140) and normal controls (n = 120) and their first-degree biologic relatives. Information on PDICs was obtained from mothers in a standardized manner blind to the proband's clinical status. Using linear and logistic regression models, a positive association was found between ADHD and PDICs in the probands. Additionally, PDICs were associated with the correlates of ADHD (i.e., impaired cognitive functioning and poor school performance). Moreover, it was those specific complications that reflect chronic exposure, such as maternal bleeding, smoking, family problems, and illicit drug use during pregnancy that accounted for these findings. No interaction between genetic factors and PDICs were found. Our findings add to the literature supporting an association between ADHD and PDICs. Our results may help clinicians focus on particular complications rather than the wide range of possible perinatal complications.