The drug susceptibility testing performance of a broth-based method with microscopic reading of bacillary growth, the microscopic observation drug susceptibility (MODS) assay, was compared to that of the reference 7H10 agar method of proportion by using 53 isolates of Mycobacterium tuberculosis from persons at risk for multidrug-resistant TB. For isoniazid (0.1 micro g/ml) and rifampin (2.0 micro g/ml), there was 100% agreement between MODS results read at day 11 and the reference method. Levels of agreement for ethambutol tested at 2.5 and 7.5 micro g/ml were 70 and 58%, respectively. Levels of agreement for streptomycin tested at 2.0 and 6.0 micro g/ml were 77 and 51%, respectively. For isoniazid and rifampin drug susceptibility testing, MODS is as accurate as and more rapid than the reference method.