Drug-resistant tuberculosis is increasing day by day and is a significant threat to tuberculosis control because there are few drugs effective against Mycobacterium tuberculosis. This study evaluates the resistance of the microorganism to primary anti-tuberculosis drugs over the 21-y period 1976-97. Records from the bacteriology laboratory of the Department of Chest Diseases and Tuberculosis, Ankara University Medical Faculty were evaluated retrospectively. Among 3,418 mycobacteria strains, 3,319 (97.1%,) M. tuberculosis were isolated and their susceptibility was examined by the proportion method in Loewenstein-Jensen medium. It was found that 60.8% of isolated strains were susceptible, whereas 39.2%, were resistant to at least one drug. Multi-drug resistant tuberculosis (MDR-TB) was found in 194 (5.8%) materials. Over the 21-y period studied, total resistance to isoniazid (INH), rifampicin (RF) and streptomycin (SM) were determined as 10.5, 6.9 and 7.0%, respectively. It was also observed that the resistance rates to INH or SM increased, whereas resistance to RF was not changed within this period. While resistance to the 2-drug combination RF+SM increased, resistance to INH+SM decreased significantly. There was no change in resistance to the 2-drug INH + RF or 3-drug INH + RF + SM combinations in the same period. In conclusion, combined therapy is still useful and available for the treatment of resistant tuberculosis, and INH should be included in the chemotherapeutic regimen even if high resistance rates are shown to exist.