The aim of this research is to evaluate current and lifetime psychiatric morbidity according to ICD-10 criteria of subjects in treatment for psychoactive substance dependence. It is a cross-sectional clinical-epidemiological study also collecting retrospective information by means of structured diagnostic interviews. Ninety-nine outpatients fulfilling criteria of eligibility were recruited by systematic sampling at 8 Italian National Health Service's Drug Dependence Units. Criteria of inclusion were the presence of clinical diagnosis of psychoactive substance dependence according to ICD-10 and age 18-45, while criteria of exclusion were pharmacological distress related to acute withdrawal from street drugs and the presence of severe cognitive impairment, delirium or acute psychoses in order to assure reliability of the interviews. Only 75 patients accepted to participate, were enrolled in the study and interviewed by means of a European adaptation of the Addiction Severity Index. Finally, the Composite International Diagnostic Interview was completed in 65 cases. The prevalence of current psychiatric morbidity for any disorder in addition to substance use disorders was 22.2%, and lifetime prevalence was 35.4% (but, if drop-out cases are excluded from calculation, the prevalence rates grow up to 30-35% and 50-55% respectively). Psychiatric morbidity is more frequent among females and is unrelated to age or lifetime duration of substance use. In almost one-half of the cases mental disorders arose before the beginning of substance use. By order of frequence, anxiety, affective, and schizophrenic syndromes are the most common comorbid diagnoses. Affective disorders are more often secondary, since they mostly develop after the beginning of psychotropic substance use and are uncommon among currently abstinent subjects. Finally, outpatients affected by psychotic disorders are not likely to abstain from psychotropic drugs during the treatment. Psychiatric comorbidity is a considerable point in the clinical management of drug dependence, and for primary and secondary prevention of substance use disorders.