Substance users have high prevalence rates of disorders that encompass multiple comorbidities, as well as varied substance use and dependence patterns. Prevalence rates of DSM-III-R antisocial personality (ASP) and other comorbid disorders were investigated among a large sample of substance-dependent treatment clients participating in a national, multisite, prospective study of substance users admitted to treatment. Subjects included 7402 substance-dependent clients with an approximate demographic makeup of 66% male, 47% African American, 12% Hispanic, and average age of 32.6 years. Subjects were assessed with modules for substance dependence and for ASP, depressive, and anxiety disorders from the Composite International Diagnostic Interview and the Diagnostic Interview Schedule. Prevalence rates for substance-dependent subjects were 39.3% ASP and 13.9% lifetime Axis I disorders, and these rates differed according to drug-dependency patterns, Logistic regression was used to assess differences among seven drug-dependency groups while controlling for differences in age, gender, and race/ethnicity, Interrelationships among ASP, other comorbid disorders, and drug-dependency patterns were evident and indicative of the need for multivariate models to better understand the consequences of these comorbid impairments.