Contact tracing, the evaluation of persons who have been in contact with patients having tuberculosis, is an important component of tuberculosis control. We used DNA fingerprinting to test the assumption that tuberculosis in contacts to active cases represents transmission from that person. Cases of tuberculosis in San Francisco between 1991 and 1996 with positive cultures who had been previously identified as contacts ("contact cases") to active cases ("index cases") were studied. Of 11,211 contacts evaluated, there were 66 pairs of culture-positive index and contact cases. DNA fingerprints were available for both members of these pairs in 54 instances (82%). The index and contact cases were infected with the same strain of Mycobacterium tuberculosis in 38 instances (70%; 95% CI: 56 to 82%); 16 pairs (30%) were infected with unrelated strains. Unrelated infections were more common among foreign-born (risk ratio [RR] = 5.22, p < 0.001), particularly Asian (RR = 3.89, p = 0.002) contacts. Contact investigation is an imperfect method for detecting transmission of M. tuberculosis, particularly in foreign-born persons. However, because such investigations target a group with a high prevalence of tuberculosis and tuberculous infection, these efforts remain an important activity in the control of tuberculosis.