OBJECTIVE: The goals of this study were to explore gender differences in demographic variables, psychiatric comorbidity, and personality disorders in individuals with substance use disorders. METHOD: A total of 100 treatment-seeking substance users (50 men and 50 women) admitted to a university-based and a university-affiliated private chemical dependency hospital were compared with regard to demographic variables and comorbid psychiatric and personality diagnosis according to the Structured Clinical Interview for DSM-III-R after 14-21 days in treatment. RESULTS: Men were significantly more likely to have a higher household income and to be alcohol dependent. Women were significantly more likely to have another axis I disorder in addition to substance use disorder, particularly anxiety disorders, but these gender differences were not substantially different from the gender prevalence of these disorders in the general population. Men had more affective disorders relative to women than would be expected from the general population data. Female alcoholics had substantially more psychopathology than male alcoholics, and generally these differences were consistent with the ratios of these disorders in the general population. For cocaine users, female/male ratios of anxiety and affective disorders were inconsistent with general population ratios and indicated more psychopathology than would be expected in male cocaine users. There were no gender differences in axis II diagnoses. CONCLUSIONS: Some of the gender differences in psychopathology in substance users are at odds with gender differences for psychopathology in the general population. Further exploration of these differences could have important theoretical and treatment implications.