IFN-gamma responses to Mycobacterium tuberculosis specific antigens are used as in vitro diagnostic tests for tuberculosis infection. The tests are sensitive and specific for latent and active tuberculosis disease, but sensitivity may be reduced during immunosuppression. The objective of the study was to explore new ways to improve the diagnosis of tuberculosis infection using CXCL10 and IL-2 as alternative markers to IFN-gamma. CXCL10, IL-2, and IFN-gamma responses to stimulation with ESAT-6/CFP10/TB7.7 were assessed in 12 Quantiferon positive, 8 Quantiferon negative tuberculosis patients and 11 Quantiferon negative controls. CXCL10 and IL-2 were determined by multiplex and IFN-gamma by the Quantiferon ELISA. The median antigen specific CXCL10, IFN-gamma, and IL-2 responses in patients with tuberculosis were 870 pg/ml (range 261-1576 pg/ml), 217 pg/ml (81-1273 pg/ml), 59 pg/ml (14-276 pg/ml) respectively, and the CXCL10 responses were significantly higher than any of the other cytokines measured (p=0.001). In 4/7 individuals with a negative (n=6) or indeterminate (n=1) Quantiferon test, antigen specific CXCL10 responses were detectable at high levels ranging from 196-532 pg/ml. In conclusion CXCL10 was strongly induced after M. tuberculosis specific stimulation and sensitivity appeared superior to the Quantiferon test. Our findings suggest that CXCL10 may serve as an alternative or additional marker for the immunodiagnosis of tuberculosis.