The relationship between substance use disorders and comorbid psychiatric conditions was investigated among 425 persons in drug treatment who met DSM-III-R criteria for drug dependence. Using the NIMH Diagnostic Interview Schedule to ascertain DSM-III-R psychiatric disorders among these drug dependent subjects, lifetime prevalence rates were 64% for alcohol abuse/dependence, 44% for antisocial personality disorder, 39% for phobic disorders, 24% for major depression, 12% for dysthymia, and 10% for generalized anxiety disorder. We found that antisocial personality disorder and phobias generally had onsets prior to the onset of drug dependence (that is, they were primary disorders). The majority of drug dependent persons with generalized anxiety disorder reported an onset after the onset of drug dependence (that is, they had secondary generalized anxiety). Alcohol dependence, depression, and dysthymia were divided nearly evenly between earlier (primary disorder) and later (secondary disorder). These results are consistent with the body of literature indicating the importance of antisocial syndromes in the etiology of substance abuse and the literature indicating the complex, varying nature of the relationship of psychiatric disorders to substance dependence. Finally, a precise nomenclature for "age of onset," "primary," and "secondary" was developed for this study that is critical to understanding these issues and is recommended for other studies.