The study investigates changes in psychiatric symptoms after drug dependence treatment, and relationships between pretreatment problems, illicit drug use, treatment retention, and changes in psychiatric symptoms. The sample comprised 662 drug-dependent adults recruited at admission to treatment in residential rehabilitation programs (15 agencies) or outpatient methadone treatment (16 methadone maintenance programs and 15 methadone reduction programs). Using a longitudinal, prospective cohort design, data were collected by structured interviews at intake to treatment and at 1-month and 6-month follow-ups. Reductions were found in a range of psychiatric symptoms after admission to drug dependence treatment and among patients treated in outpatient and in residential programs. These reductions occurred rapidly (during the first month) and were maintained at subsequent follow-up. At intake to treatment, 39% of the residential sample met criteria for psychiatric caseness. This figure dropped to 3% at both 1-month and 6-month follow-up. Among methadone patients, 15% met criteria for psychiatric caseness at intake, and this dropped to 5% at 1 month and 3% at 6 months. Improvement in psychiatric symptoms was positively related to treatment retention. Some of the psychiatric symptoms presented by drug-dependent patients at admission to treatment are associated with drug misuse and show rapid remission after substance misuse treatment.