Purpose: To examine the link between symptoms of hyperactivity-inattention and conduct disorder in childhood, and the initiation of tobacco and cannabis use, controlling for other behavioral symptoms, temperament and environmental risk factors. Method: The sample (N = 1107 participants, aged 4 to 18 years at baseline) was recruited from the population-based longitudinal Gazel Youth study with a follow-up assessment 8 years later. Psychopathology, temperament, environmental variables, and initiation of tobacco and cannabis use were self-reported. Event time analyses were performed to assess the effects of childhood disruptive symptoms on age at first use of tobacco and cannabis. Results: Proportional hazard models revealed that participants with high levels of childhood symptoms of both hyperactivity-inattention and conduct disorder were at highest risk of early tobacco initiation (in males: hazard ratio [HR]= 2.05; confidence interval [CI]: 1.24-3.38; in females: HR = 2.01; CI: 1.31-3.09), and, in males, of early cannabis initiation (HR = 1.95; CI: 1.04-3.64). Temperament, through activity in both males and females and negative emotionality in females, was also associated to early substance use initiation. Conclusions: Children who simultaneously have high levels of symptoms of hyperactivity-inattention and conduct disorder are at increased risk for early substance initiation. These associations may guide childhood health professionals to consider the liability for early substance initiation in high-risk groups. (C) 2010 Elsevier Masson SAS. All rights reserved.