We evaluated the utility of the "QuantiFERON-TB Gold In-Tube" (QuantiFERON) test that uses tuberculosis (TB)-specific antigens for the diagnosis of latent infection in such individuals. We also examined the correlation between the interferon (IFN)-gamma response to these antigens and the exposure risk to TB by evaluating antigen-specific IFN-gamma release in comparison with IFN-gamma release in response to purified protein derivative (PPD) in 3 groups: medical students, nurses in a TB hospital, and TB patients. All nurses and TB patients responded to PPD, whereas 52% (P < 0.0001) and 79.2% (P = 0.04) responded to QuantiFERON, respectively. In the medical students, only 10.4% responded to QuantiFERON, whereas 85.2% were positive to PPD (P < 0.0001). There was also a significant correlation between the levels of IFN-gamma production and the duration of employment in the group of nurses at the TB hospital, suggesting ongoing exposure in this high-risk group. Thus, these results demonstrate that Mycobacterium tuberculosis-specific IFN-gamma release assay accurately discriminates low- and high-risk healthy subjects and might therefore be a useful diagnostic tool for the diagnosis of latent infection in Bacille Calmette-Guerin (BCG)-vaccinated individuals.