On September 30, 1999, the Food and Drug Administration approved a reformulated Amplified Mycobacterium Tuberculosis Direct Test (MTD) (Gen-Probe, San Diego, California) for detection of Mycobacterium tuberculosis in acid-fast bacilli (AFB) smear-positive and smear-negative respiratory specimens from patients suspected of having tuberculosis (TB). MTD and one other nucleic acid amplification (NAA) test, the Amplicor Mycobacterium Tuberculosis Test (Amplicor) (Roche Diagnostic Systems, Inc., Branchburg, New Jersey), previously had been approved for the direct detection of M. tuberculosis in respiratory specimens that have positive AFB smears. This notice updates the original summary published in 1996 (1) and provides suggestions for using and interpreting NAA test results for managing patients suspected of having TB. The appropriate number of specimens to test with NAA will vary depending on the clinical situation, the prevalence of TB, the prevalence of nontuberculous mycobacteria (NTM), and laboratory proficiency (2,3). Based on available information, the following algorithm is a reasonable approach to NAA testing of respiratory specimens from patients with signs or symptoms of active pulmonary TB for whom a presumed diagnosis has not been established.