Understanding human immune responses in chronic refractory tuberculosis (CRTB) is important for developing immunotherapy against the disease. the aim of this study was to examine cytokine responses [interferon (IFN)-$gamma$, tumor necrosis factor (TNF)-$alpha$, interleukirl (IL)-6, and IL-10] by peripheral blood mononuclear cells (PBMCs) in CRTB patients after in vitro stimulation with the 30-kDa or purified protein derivative (PPD) antigen (Ag). Most of the CRTB cases were multidrug-resistant (MDR) TB. The results were compared with those from early TB (E-TB) patients and healthy tuberculin reactors (HTR). IFN-$gamma$ production was significantly depressed in both CRTB and E-TB groups compared with HTR. In response to the 30-kDa Ag, TNF-$alpha$ levels were significantly depressed only in CRTB patients, while greatly increased in E-TB patients. In addition, IL-10 production was significantly increased in E-TB patients, and PBMC from both E-TB and CRTB patients secreted more IL-6 than HTR. IL-10 neutralization significantly increased TNF-$alpha$ levels, whereas anti-TNF-$alpha$ did not alter IL-10 induction significantly in PBMC from HTR and CRTB patients. Our findings suggest that CRTB patients have depression in both IFN-$gamma$ and TNF-$alpha$ reponses, which might play important roles during chronic M. tuberculosis infection.