A study was performed to assess the risk of drug-dependent persons for developing tuberculosis. Tuberculosis prevalence was 3,740/100,000 drug-dependent inpatients compared with 584/100,000 non-drug-dependent discharges. In another program, prevalence was 3,750/100,000; in the New York Methadone Program, prevalence was 2,652/100,000 patients in Harlem and 1,372/100,000 city-wide. The city-wide prevalence rate in the entire population was 86.7/100,000 in 1971 and 64.7/100,000 in 1973. Similar elevations in incidence also were found in drug-dependent vs non-drug-dependent populations. Our data show that disease rate is elevated in drug-dependent populations, suggesting that drug dependency reflects a high-risk situation for tuberculous infected individuals developing tuberculosis disease. We suggest that infected drug-dependent persons (tuberculin positive) be considered for preventive therapy with isoniazid, which can be piggybacked onto a drug treatment program.