Objective: This study demonstrates the value of Mycobacterium tuberculosis fingerprinting used in conjunction with traditional epidemiologic methods to identify smoldering outbreaks of tuberculosis in endemic areas where background rates of tuberculosis are high. Methods: IS6110 DNA fingerprinting was performed on isolates of M tuberculosis from verified cases of tuberculosis in Alabama from 1994 to 1998. A statewide database groups isolates into "clusters" and tracks them cumulatively over time. A large cluster was identified and was secondarily investigated using traditional epidemiologic methods. Results: Twenty-five isolates were found to be identical by fingerprinting analysis. Patients were living within 10 counties across the state, and 12 cases were localized to a single county. This represented an ongoing, statewide tuberculosis outbreak previously unrecognized by local and state health officials. Secondary investigation of the cases revealed the primary sites of transmission to be a correctional facility and two homeless shelters. Conclusions: Population surveillance using M tuberculosis fingerprinting was successfully utilized to detect a significant and smoldering tuberculosis outbreak. Measures are currently in place to identify and prevent further transmission in the involved locations.