RATIONALE: Human immunodeficiency virus (HIV) infection has a major but unquantified impact on the risk of tuberculosis. OBJECTIVES: To quantify the impact of HIV infection on the number of tuberculosis cases in San Francisco. METHODS: We studied all patients reported with tuberculosis in San Francisco from 1991 to 2002. The initial isolates of Mycobacterium tuberculosis were genotyped using IS6110 restriction fragment-length polymorphism genotyping as the primary method, and clustered cases (identical genotype patterns) were identified. MEASUREMENTS AND MAIN RESULTS: We determined the case number, case rate, and the fraction of tuberculosis attributable to HIV infection. Of 2,991 reported tuberculosis cases, 2,193 (73.3%) had a genotype pattern of M. tuberculosis available. Genotypic clusters with at least one HIV-positive person were larger, lasted longer, and had a shorter time between successive cases relative to clusters with only HIV-uninfected persons (P < 0.00005, P = 0.0009, P = 0.018, respectively). Overall, 13.7% of the tuberculosis cases were attributable to HIV infection and an estimated 405 excess tuberculosis cases occurred. CONCLUSIONS: During a period encompassing the resurgence and decline of tuberculosis in San Francisco, a substantial number of the tuberculosis cases were attributable to HIV infection. Coinfection with HIV amplified the local tuberculosis epidemic.