The tuberculin skin test used to detect latent Mycobacterium tuberculosis infection has many drawbacks, and a new diagnostic test for latent tuberculosis (QuantiFERON-TB [QTF-TB]) has recently been introduced. This test measures the production of IFN-gamma in whole blood upon stimulation with purified protein derivative (PPD). The QTF-TB test addresses the operational problems with the tuberculin skin test, but, as the test is based on PPD, it still has a low specificity in populations vaccinated with the Bacille Calmette-Guérin (BCG) vaccine. We have modified the test to include the antigens ESAT-6 and CFP-10, which are not present in BCG vaccine strains or the vast majority of nontuberculous mycobacteria. This test was used to detect infection in contacts in a tuberculosis outbreak at a Danish high school. The majority of the contacts were BCG-unvaccinated, which allowed a direct comparison of the skin test and the novel blood test in individuals whose skin test was not confounded by vaccination. An excellent agreement between the two tests was found (94%, kappa value 0.866), and in contrast to the blood test based on PPD, the novel blood test was not influenced by the vaccination status of the subjects tested.