The morbidity, mortality, and relapse rates of tuberculosis have increased in the Russian Federation since 1991. Increased drug resistance may be one reason for the weakened efficacy of local tuberculosis treatments. Laboratory data on tuberculosis resistance were collected from a survey area that included two republics and seven other administrative regions (oblasts) with a total population of more than 14 million. Susceptibility data from 1991 through 1994 were available from all nine regions; data on resistance to individual drugs and data from 1984 through 1994 were available from the Leningrad region and the city of St. Petersburg. From 1991 through 1994. the annual notification rate of tuberculosis increased in the survey area by 53.7% (from 25.1 to 38.6 cases per 100000 inhabitants), tuberculosis mortality doubled (from 4.4 to 9.2 deaths per 100000), and primary resistance to at least one drug increased from 17% (95% CI, 14.9-19.9) to 24% (95% CI, 22.2.-25.8). The prevalence of primary resistance to at least isoniazid and rifampin (multidrug resistance) was 5.1% in the Leningrad region in 1992 through 1994. The proportion of pulmonary isolates with secondary multidrug resistance increased from 21.6% (95% CI 7.9-25.3%) in the period 1984-1994 to 33% (95% CI 29.7-36.3%) in 1989-1994. Even if these figures are biased upwards because of selection, it can be concluded that secondary resistance to tuberculosis drugs was already prevalent in northwestern Russia ten years ago. Since then, a distinct shift towards multidrug resistance has occurred. The lower prevalence of primary multidrug resistance raises hopes that the resistance problem can be controlled with properly designed and monitored therapeutic measures.