This investigation examined variables that might qualify or detail the widely accepted relation between negative affectivity and drug use in adolescent boys. In Study 1, 311 boys (15-17 years old) completed inventories of negative affectivity, positive affectivity, constraint, delinquency, peer delinquency, and drug use. Negative affectivity was positively related to drug use, but only for individuals exhibiting high peer delinquency or low constraint. Study 2 examined mechanisms for this relation by following up 143 of the participants at ages 17-20 years. Delinquency and peer delinquency mediated the relation between negative affectivity and later drug use. These findings suggest that the relation between negative affectivity and drug use is best understood within the context of other drug use risk factors.