The objective of the study was to investigate the characteristics of adults with Attention Deficit Hyperactivity Disorder (ADHD) or substance use disorder (SUD), especially in the context of comorbid psychiatric disorders. Subjects were adults (n = 78) participating in a controlled family study of ADHD and SUD. Four groups were identified based on a diagnosis of ADHD or SUD: ADHD, SUD, ADHD + SUD, and neither ADHD nor SUD. All diagnoses were determined by structured clinical interview for DSM IV. Rates of psychiatric comorbidity were lowest in the controls, intermediate in the ADHD and SUD groups, and highest in the ADHD + SUD group. Relative to controls, the ADHD, SUD, and ADHD + SUD groups had higher rates of major depression (z = 1.98, p = 0.05), conduct disorder (z = 2.0, p = 0.04), antisocial personality disorder (z = 2.6, p = 0.009), agoraphobia (z = 2.5, p = 0.01) and social phobia (z = 2.7, p = 0.007). Higher rates of psychiatric comorbidity, especially mood and anxiety disorders, exist in subjects with SUD + ADHD relative to subjects with SUD, ADHD, or controls. Clinicians need to be attentive to other psychiatric disorders that may occur in the large group of adults with ADHD + SUD.