Isoniazid resistance in Mycobacterium tuberculosis is associated with lack of catalase-peroxidase activity. A recent study showed that some isoniazid-resistant M. tuberculosis strains have a complete deletion of the gene (katG) encoding this enzyme. To examine what proportion of clinical isolates of M. tuberculosis have katG deletion, katG sequences in 80 randomly selected isolates from New York City were analyzed. Polymerase chain reaction was used to amplify a 282-bp segment of M. tuberculosis katG and showed that 35 (90%) of 39 isoniazid-sensitive and 31 (76%) of 41 isoniazid-resistant strains contained katG sequences (P > .1). Ten multidrug and high-level isoniazid-resistant strains with identical restriction fragment length polymorphism patterns were also analyzed. All were found to have katG sequences. These findings suggest that mechanisms other than complete deletion of katG are involved in isoniazid resistance among most clinical isolates of M. tuberculosis from New York City.