Between 1991 and 1993, 444 inhabitants of the metropolitan area of Zurich were reported as confirmed or suspected cases of tuberculosis (TB). Overall, isolates of Mycobacterium tuberculosis of 361 patients (90% of the bacteriologically confirmed cases) were available to study the frequency of transmission of the strains on a molecular level. Restriction fragment length polymorphism (RFLP) analysis was performed by using IS6110 and the polymorphic GC-rich sequence (PGRS) as genetic markers. Ninety nine isolates shared by 77 patients (21.3%) were associated with 28 IS6110-defined clusters. However, secondary typing of low copy number isolates decreased the number of clusters to 25, encompassing 81 isolates from 63 (17.5%) patients. By deoxyribonucleic acid (DNA) fingerprinting plus conventional contact tracing, definite transmission of TB was proven in only five patients (1.4%) and assumed in 20 patients (5.6%). In all other cluster-associated isolates, no epidemiological connections between the patients could be found using the clinical and sociodemographic data available. The present study demonstrates that in the time period studied only minor transmission occurred.