This study aimed to evaluate the concurrent and lifetime psychiatric comorbidity and drug use patterns in patients admitted to the hospital for detoxification from benzodiazepines. Psychiatric assessments using the Structured Clinical Interview for DSM-III-R with a psychosis screening module (SCID-P and II) were conducted in 30 inpatients admitted to the medical unit treatment unit of the Clinical Research and Treatment Institute of the Addiction Research Foundation for the treatment of severe benzodiazepine dependence. Patients (mean age, 36 years; range, 22-58; number of DSM-III-R criteria met for benzodiazepine substance dependence, > or = 7 out of 9 [73%], all 9 criteria [40%]) used benzodiazepines and other drugs over prolonged periods of time at high doses, and their daily functioning was substantially impaired (Mean Global Assessment of Functioning Score, 48; range, 31-60). The most common lifetime psychiatric diagnoses were major depression (33%), other psychoactive drug dependence (100%) (opioids, 77%; alcohol, 53%), and panic disorder (30%). Current psychiatric diagnoses in addition to benzodiazepine dependence included other psychoactive substance use disorders (83%) (opioids, 67%; cocaine, 13%; multiple concurrent substance use, 17%), panic disorder (13%), and generalized anxiety disorder, (20%). Personality disorders included antisocial (42%), avoidant (25%), and borderline (17%). These findings demonstrate that in patients severely dependent on benzodiazepines, additional psychoactive substance use and mental disorders are prominent. The pattern of drug use and psychiatric comorbidity differentiates these patients from therapeutic-dose benzodiazepine users.