Studies report increased rates of cigarette and substance use in youths with Attention-Deficit/Hyperactivity Disorder (ADHD), though the mechanism of risk remains unclear. The present study tests the hypothesis that ADHD individuals "self-medicate" with cigarettes and substances of abuse. As part of five- and ten-year case-control longitudinal family studies of ADHD, responses to the Drug Use Screening Inventory (DUSI) were examined for evidence of self-medication. DUSI data from 90 ADHD probands and 96 control probands were obtained. Thirty-six percent of subjects reported self-medication, 25% used to get high, and 39% had unknown motivation. No significant differences were found between ADHD and controls in motivation. ADHD symptoms did not differ between self-medicators and subjects using to get high. DUSI problem scores were higher in ADHD (versus controls), those using to get high (versus self-medicators), and subjects using alcohol (versus other substances). More than one-third of adolescents and young adults endorsed using cigarettes and substances for self medication. Studies clarifying the role of self-medication in substance use disorders are necessary.