Causes of community-acquired bloodstream infections (BSIs) in sub-Saharan Africa are unknown with regard to mycobacteria and fungi. We prospectively studied 517 consecutive febrile (axillary temperature, > or =37.5 degrees C) adults (> or =15 years of age) admitted to one hospital in Tanzania. After hospital admission and informed consent, blood was drawn for culture (of bacteria, mycobacteria, and fungi), determination of human immunodeficiency virus type 1 (HIV-1) status, and malaria smears. Malaria smears were prepared for a control group of 150 afebrile patients. One hundred and forty-five patients (28%) had BSI. Of these 145 patients, 118 (81%) were HIV-1-infected. HIV-positive patients were more likely than HIV-negative ones to have BSI (118 of 282 vs. 27 of 235; P < .0001). The three most frequently isolated pathogens were Mycobacterium tuberculosis (60 [39%]), non-typhi Salmonella species (29 [19%]), and Staphylococcus aureus (13 [8.3%]). The incidence of malaria parasitemia was similar in study and control patients (9.5% vs. 8%). In this patient population with high prevalence of HIV-1 infection, M. tuberculosis has become the foremost cause of documented BSI.