Vγ9/Vδ2 T cells can contribute to protective immune response against Mycobacterium tuberculosis although the extent to which and mechanisms by which they could actually protect against human tuberculosis remain unclear. We have previously reported that Vγ9/Vδ2 T cells from tuberculin purified protein derivative (PPD)–positive children, either healthy or affected by different clinical forms of tuberculosis, strongly proliferate to different phosphoantigens in vitro, whereas Vγ9/Vδ2 T cells from PPD-negative healthy subjects proliferate very poorly. We report here that Vγ9/Vδ2 T cells from tuberculous children have an increased proliferative activity, but decreased interferon (IFN)–γ production and granulysin expression. After successful chemotherapy, the Vγ9/Vδ2 T cell proliferative response strongly decreased, whereas IFN-γ and granulysin production consistently increased. Disease-associated changes in Vγ9/Vδ2 T cell effector functions in patients with tuberculosis are consistent with the possibility that these T cells may play a protective role in immune response against M. tuberculosis infection