We aimed to determine the present status of drug resistance of Mycobacterium tuberculosis at the Gaziantep University Hospital in south-east Turkey. Data for 1995 to 1999 were retrospectively evaluated with respect to smear-positive cases, first positive culture for Mycobacterium tuberculosis for each patient and drug-susceptibility tests for the major antituberculous drugs. Cultures were done using the Bactec 460 TB method. A total of 106 (40.2%) strains were resistant to at least one drug. Single drug resistance was observed in 47 strains (17.8%) and resistance to two or three drugs was found in 28 and 29 strains (10.6 and 11.0%), respectively. Two strains (0.8%) were resistant to all four drugs. While multidrug resistance was observed in 52 (19.7%) strains, resistance to isoniazid + rifampin was observed in 20 (7.6%) strains. This retrospective study showed that combined drug resistance of hi. tuberculosis is highly prevalent in southeastern Turkey. Possible reasons for the failure of current control policies were considered.