Molecular profiling of Mycobacterium tuberculosis isolates has improved recognition of tuberculosis case clusters, but the determinants of cluster size are unknown. We hypothesized that longer duration of symptoms prior to initiation of tuberculosis therapy would be associated with increased cluster size. All patients with tuberculosis in Harris County, Texas, identified between 10/1/95 and 12/31/97 through a prospective population-based project were interviewed, had their medical records reviewed, and had M. tuberculosis isolates molecularly characterized. There were 506 symptomatic, evaluable patients in 74 clusters, ranging in size from 2 patients (32 clusters) to 61 patients (1 cluster). The median duration of symptoms was 46 days (range, 1-471 days). There was no association between the log-transformed duration of symptoms and cluster size in univariate or multivariate analysis. In multivariate analysis, age and HIV coinfection were inversely related to cluster size, but only weakly. The size of molecularly defined clusters of tuberculosis was not related to the duration of symptoms of most patients who belonged to clusters.