A community-based study of tuberculosis in Santa Clara County, California was conducted in order to identify community-specific determinants of drug-resistant Mycobacterium tuberculosis infections. From January 1984 through December 1986, 517 verified cases of tuberculosis were reported from the county. Drug susceptibility test results to isoniazid, streptomycin, ethambutol, and rifampin were available for 256 of the 517 cases. The frequency of resistance of M. tuberculosis isolates to one or more drugs was 27% for all cases and 25% for those who had had no previous antituberculosis treatment. Isolates from Asian immigrants had the highest frequencies of resistance (33 to 45%), and the Southeast Asian immigrants had a drug-resistant tuberculosis case rate greater than 30/100,000 population per year. In patients who had cavitary lung disease and who had a previous history of tuberculosis, drug-resistant tuberculosis was 3.5 times as likely to occur than in persons who had neither of these characteristics (p less than 0.001). For such patients, the positive predictive value of isolating resistant M. tuberculosis approached 90%. We believe these community-based findings will guide clinical and public health interventions specifically appropriate for the community.