Earlier data suggest that γ/δ T cells may play an important role in the immune response to Mycobacterium tuberculosis. The aim of this study was to determine the percentage of different γ/δ subsets in peripheral blood of active tuberculosis patients with a positive or negative tuberculin reaction. Thirty-eight patients infected with M. tuberculosis and 22 healthy controls were included in the study. Venous blood was taken before starting antimycobacterial treatment. Lymphocytes were reacted with monoclonal antibodies specific for different γ/δ V chains (Vδ1, Vδ2, Vγ9 and Vγ4). The results were analysed in the context of tuberculin reactivity and X-ray findings. Our results revealed a selective loss of Vγ9/Vδ2 T cells in the peripheral blood of tuberculin-negative patients with active tuberculosis compared to healthy controls, while the ratio of Vγ9/Vδ2 T cells in the peripheral blood of patients with a positive skin test did not differ from that of healthy controls. These findings demonstrate a relationship between the loss of the major M. tuberculosis-reactive subset of γδ T cells and the absence of tuberculin reactivity. The data are consistent with the hypothesis that γδ T cells play a role in the protective immune response to M. tuberculosis infection.