- Study objectives To assess the incidence of tuberculosis in the native and immigrant populations of southern Israel in the period between 1992 and 1997, and to study the prevalence of drug resistance overall and among these subpopulations in the region in order to create guidelines for empirical antituberculous treatment in this region. Design A retrospective population-based study. Setting The southern district of the country and its tertiary-care hospital. Patients All new culture-proven tuberculosis cases diagnosed in adults residing in the Negev region during the study period. Patients were classified into four groups according to ethnic origin and immigration date. Results During the study period, 249 new cases involving 249 patients were recorded. Immigrants from the former Soviet Union (IFSU) were significantly younger and of male gender, and the incidence among this group rose sharply. IFSU had higher rates of resistance to any drug or drug combination. Isoniazid resistance rates were 16% overall and 32% among IFSU. Resistance to any drug was observed in 29% overall and 50% of isolates among IFSU. Multidrug-resistant tuberculosis was observed in 8.5% and 17%, respectively. Conclusions The population of southern Israel carries very high rates of drug-resistant tuberculosis, mandating quadruple empiric treatment. IFSU should be regarded as having multidrug-resistant tuberculosis until proven otherwise, and empiric therapy with at least five drugs should be considered. This report demonstrates the influence of immigration on the incidence of tuberculosis, and the great value of local surveillance of population-specific resistance rates in an immigrant society, in order to optimize drug treatment and prevent the dissemination of resistant strains.