The influence of psychiatric comorbidity on the course and outcome in a nationwide representative sample (n = 351) of treatment-seeking substance users over a 28-month period was studied prospectively. The patients were administered the Diagnostic Interview Schedule and a questionnaire on drinking history. At 16 and 28 months after admission rite patients returned a questionnaire on drinking history and mental health. In cases of those lacking information on either follow-up (45%), details on drinking status was obtained from informants, Completely abstinent were 16%, Generalized anxiety disorder and/or social phobia at the index admission predicted abstinence during the follow-up [odds ratio (OR) = 0.25], whereas onset of alcoholism among these patients after age 25 years predicted a worse prognosis (OR = 13.5). Also increasing number of social consequences related to abuse (OR = 1.3) and drinking more than the median (OR = 2.1) predicted a poor outcome. The abstinent group had significantly better mental health al follow-up. The patients with comorbid psychiatric disorders at admission were worse at follow-up. Although substance use disorders and comorbid psychiatric disorders have to a certain degree separate courses. there is nevertheless significant interaction between them. Early treatment and recognition of comorbid psychiatric disorders among substance abusers is necessary.