To assess the frequency and etiology of fever of uncertain origin (FUO) in patients infected with the human immunodeficiency virus (HIV) and to evaluate the yield of diagnostic procedures used in their evaluation, we reviewed the clinical charts of all patients admitted to an AIDS unit during a 15-month period. FUO was defined by the endurance of a fever (temperature, > 38.2 degrees C) for at least 4 weeks before admission and the uncertainty of diagnosis after 3 days, despite appropriate investigation. Of 580 patients evaluated, 50 (8.2%) had FUO. Patients with FUO were at advanced stages of HIV infection (median CD4+ cell count, 71/mm3), and a vast majority (84%) had previously diagnosed AIDS. A cause of the fever was identified for 44 patients (88%), and infections accounted for 82% of all cases. Tuberculosis (42%), visceral leishmaniasis (14%), and disseminated Mycobacterium avium complex infection (14%) were the most frequent diagnoses. Examination of lymph node aspirates, bone marrow biopsy, and culture of clinical specimens for mycobacteria were the procedures with the highest diagnostic yield. Among 6 patients with fever of no identified etiology, 4 died while febrile, and fever was self-limited in the other 2 patients. FUO is common among patients with advanced HIV infection. Since a cause, usually infection, can be identified in most patients, long-lasting fever should not be attributed to HIV itself.