The annual number of cases of tuberculosis in New York City has increased since 1978. In addition, in 1991 a 1-month survey of cases of tuberculosis in New York City found that 33% of all cases were resistant to at least one drug. To determine susceptibility trends from 1987 to 1991, a period during which an unprecedented rise in resistant tuberculosis occurred in New York City, we reviewed the microbiology records of 44 New York City hospitals (comprising > 14,000 cases). The percentage of cases resistant to at least one drug rose from 19% in 1987 to 28% in 1991, and the percentage of cases resistant to isoniazid rose from 13% in 1987 to 23% in 1991, while resistance to at least both isoniazid and rifampin rose from 6% to 14%. The rise of multidrug-resistant tuberculosis occurred in all four surveyed boroughs (counties) of New York City. These data demonstrate how rapidly multidrug-resistant tuberculosis can appear, and they suggest that initial empirical regimens should be broadened at certain hospitals.