Tubercolosis has increased dramatically in the United States. Noncompliance with treatment is high. The purpose of this investigation was to achieve compliance with prophylactic TB treatment and simultaneously decrease drug use in a high-risk group of intravenous drug users. Two studies were conducted. Study 1: Subjects were 9 chronic opiate users who tested positive for tubercolosis and were placed on isoniazid (INH) and methadone. Methadone was dispensed contingent upon INH ingestion throughout. A within-subject, A-B design with contingency management interventions on drug use was implemented. Results: Compliance with INH was 100% in 8 patients. Cocaine use remained high. Study 2: Two patients, meeting same criteria as Study 1, participated in a within-subject A-B multiple baseline design. Methadone was dispensed contingent upon INH ingestion throughout. Successive decreases in cocaine use were reinforced in the contingent phase. Results: Compliance with INH was high. During contingency, both patients had over 40% cocaine-free urine samples compared with 0% at baseline. This investigation serves as a model for achieving compliance with TB treatment in opiate users. © 1993.