Mycobacterium tuberculosis is one of the most successful human pathogens. Highly virulent strains, which are more easily transmitted than are less virulent strains, elicit variable immune responses. We evaluated the Th1 responses (IFN-γ production) in healthy volunteers after stimulation with various strains. Our results show that the individuals with negative tuberculin skin test (TST) results were not necessarily naive to all of the strains tested, whereas individuals with positive TST results did not respond to all of the strains tested. Drug-resistant strains induced a lower mean level of IFN-γ production than did drug-sensitive strains. One possible practical application of this finding would be for the prediction of responses to treatment, in which it might be advantageous to have knowledge of the estimated IFN-γ production elicited by a specific isolated strain.