BACKGROUND: IFN-gamma plays an important role in host response to intracellular organisms such as mycobacterium. Human infection with mycobacterium leads to a wide variety of outcomes, ranging from asymptomatic infection to widespread and rapidly fatal disease. Recent reports suggest that alteration of the function of IFN-gamma caused by a defective IFN-gamma receptor gene can explain different host response to mycobacterium. In this study, we investigated the role of IFN-gamma in the development of chronic refractory tuberculosis. METHODS: The LPS-induced TNF-alpha production with or without IFN-gamma priming was compared by using monocytes taken from recently diagnosed tuberculosis, chronic refractory tuberculosis patients and controls. And the IFN-gamma receptor was measured by indirect fluorescent antibody technique to know whether change in the priming effect of IFN-gamma is related to IFN-gamma receptor deficiency or not. RESULTS: The ratio of TNF-alpha produced in response to stimulation with INF-gamma and LPS to LPS alone was 13.5 +/- 7.6 in controls, 10.8 +/- 6.4 in recently diagnosed tuberculosis patients and 6.7 +/- 3.9 in chronic refractory tuberculosis patients. The priming effect of IFN-gamma significantly decreased in chronic refractory tuberculosis patients compared with that in controls (p=0.002). However, IFN-gamma receptor deficiency was detected in one of chronic refractory tuberculosis patients. CONCLUSION: The decrease of the priming effect of IFN-gamma may play an important role in the development of chronic refractory tuberculosis, and in some patients, this may be related to the IFN-gamma receptor deficiency.