The hypothesis that T-cell interferon-gamma responses to Mycobacterium tuberculosis-specific antigens decline as disease activity diminishes with tuberculosis (TB) treatment has generated interest in the interferon-gamma release assays (IGRAs) as treatment-monitoring tools. We studied the effect of TB treatment on these responses as measured by the QuantiFERON-TB Gold In-tube (QFT-IT) and T-SPOT.TB assays. 275 sputum culture-positive, HIV-uninfected pulmonary TB patients were tested with QFT-IT and T-SPOT.TB at baseline, treatment completion and 6 months thereafter. The QFT-IT was also performed at the end of the intensive phase. The time-treatment effect on the qualitative and quantitative IGRA results was determined. There were significant declines in the positivity rates and quantitative results of both IGRAs with treatment. The QFT-IT positivity rate was significantly lower than the T-SPOT.TB. The test reversion rate was significantly different for the two assays (13.9% for T-SPOT.TB versus 39.2% for QFT-IT). 79% and 46% tested positive with T-SPOT.TB and QFT-IT respectively at 6 months post-treatment completion. The kinetics of the quantitative responses was not significantly different between subjects with and without risk factors for disease relapse. That a substantial proportion of patients remained test-positive after TB treatment would suggest a limited role of IGRAs as treatment monitoring tools.