The current tuberculosis epidemic in the United States is marked, in many areas, by high rates of noncompliance with antituberculous regimens. In response to this, a comprehensive program of medical, nursing, social services, and supervised therapy was developed at Bellevue Hospital. Most patients were referred to the on-site directly observed therapy program (DOT) located in the hospital. Patients on DOT received daily or twice weekly therapy, and were given incentives to enhance compliance. Outreach was used to track patients who missed appointments. From November 1992 through July 1993, 113 patients were referred. HIV infection, homelessness, illicit drug use, and alcoholism were common. Follow-up revealed that 11 patients were noncompliant and completely lost to follow-up; of the remaining 102, 99% achieved bacteriologic cure. Of the 102 patients who received therapy, 74 attended the Bellevue DOT clinic, 16 attended other DOT programs in the city or received medication at home, and three died of HIV-related, nontuberculous illness. Nine patients were self-medicated and judged treatment successes. We conclude that a comprehensive hospital-based tuberculosis control program is capable of achieving a high degree of success, even in a population at high risk for noncompliance.