Objective:To determine the relationship betweenMycobacterium tuberculosisinfection and disease and subsequent disseminatedM. aviumcomplex (MAC) disease in HIV-infected persons.Design:A prospective observational cohort study.Setting:The AIDS Linked to the Intravenous Experience (ALIVE) cohort of injecting drug users and the Johns Hopkins Hospital Adult HIV Clinic (JHHAHC).Participants:HIV-infected persons aged > 18 years with CD4 lymphocytes < 100 × 106/l were followed between July 1989 and 31 October 1996. There were 182 persons in the ALIVE cohort and 1129 persons in JHHAHC who met these criteria.Main outcome measure:The relative risk of disseminated MAC was determined according to a history of prior opportunistic infection, MAC prophylaxis, antiretroviral therapy,M. tuberculosisinfection or disease, race, sex, and injecting drug use.Results:Amongst the 30 patients with active tuberculosis, eight developed disseminated MAC, compared with 208 cases of disseminated MAC amongst 1148 patients without priorM. tuberculosisinfection or disease [relative risk (RR), 1.5; 95% confidence interval (CI), 0.8–2.7;P= 0.2]. Amongst the 10 patients with extrapulmonary tuberculosis, five developed disseminated MAC (RR, 2.8; 95% CI, 1.5–5.2;P= 0.02). Injecting drug use was associated with a decreased risk of disseminated MAC (RR, 0.7; 95% CI, 0.6–0.9;P= 0.007). In a logistic regression analysis, disseminated MAC was significantly associated with extrapulmonary tuberculosis and other opportunistic disease, whereas antibiotic prophylaxis and injecting drug use were protective.Conclusions:A history ofM. tuberculosisinfection or disease was not associated with protection against subsequent disseminated MAC disease in HIV-infected persons. However, persons with extrapulmonary tuberculosis were at increased risk for disseminated MAC, particularly at low CD4 cell levels.