We describe the clinical presentation, predisposing conditions, diagnostic approach, and outcome for 52 patients with disseminated tuberculosis who presented at Duke University Medical Center (Durham, NC) from 1980 through 1999. The mean age of the patients was 52 years (range, 2-93 years). Fever and weight loss were common at presentation, and delays in the initiation of therapy often occurred. Predisposing conditions included human immunodeficiency virus infection (46% of patients), immunosuppressive therapy (21%), alcoholism (12%), diabetes mellitus (12%), and hematologic disorders (8%); 17% of patients had no disorder of immunity detected. Examination of biopsy specimens from sites of localized disease, especially lymph nodes, had a high diagnostic yield. In this study, mycobacterial blood culture appeared to be as sensitive as bone marrow culture in diagnosing disseminated tuberculosis (sensitivity, 58% vs. 54%). To diagnose disseminated tuberculosis, a search for sites of localized disease should be undertaken, and samples from these sites should be obtained. Mycobacterial blood culture can play an increasing role in the diagnosis of disseminated tuberculosis when localized disease is not found.