Tuberculosis due to Mycobacterium tuberculosis has been reported in captive elephants. Lesions most often involve the lung and associated lymph nodes. Nonspecific responses are observed on tuberculin skin tests and on some in vitro immunologic tests; therefore, diagnosis should be made on an organism-based test of trunk washes. Multidrug regimens, including isoniazid and rifampin, have been developed that eliminate shedding of M tuberculosis in discharges and minimize development of drug-resistant strains. It is important to emphasize that drug sensitivity tests should be conducted to determine the susceptibility of the organism. Also, blood concentrations should be monitored periodically to confirm they are high enough to kill the bacteria.