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To determine the proportion and distribution of drug-resistant Mycobacterium tuberculosis in California, we surveyed all California counties for drug-susceptibility test results for initial isolates from tuberculosis cases counted during the first quarters of 1991 and 1992. Overall, drug-susceptibility test results were not available for 17% of isolates. Among isolates with available test results, the proportion with resistance to isoniazid averaged 8.7%, and the proportion with resistance to at least 2 drugs, multidrug resistance, averaged 5.9% during these two quarters. The proportion of isolates with drug resistance did not change substantially during these time periods. The proportion with combined isoniazid and rifampin resistance remained stable at about 1.1%. Among persons whose isolates were tested for drug resistance, those with a known previous diagnosis of tuberculosis (relative risk [RR] = 2.6; 95% confidence interval [CI], 1.6 to 4.3; P < .01) and persons who were foreign born (RR = 1.7; 95% CI, 1.1 to 2.7; P = .014) were more likely to have isoniazid-resistant organisms. These statewide data suggest that the initial tuberculosis treatment regimen in California should include 4 antituberculosis drugs, as recommended by the American Thoracic Society and the Centers for Disease Control and Prevention for areas with a prevalence of isoniazid resistance of 4% or greater. The lack of test results for 1 in 6 patients with tuberculosis suggests the need for improved physician and laboratorian education to implement the recommendations that drug susceptibility be tested on all initial isolates.