BACKGROUND Fever is common among persons with human immunodeficiency virus (HIV) infection. However, the clinical implications of fever in this population have not been evaluated. We therefore undertook a prospective study of fever in persons with advanced HIV infection to determine the incidence and etiology of fever in this patient group. METHODS Prospective natural history study of 176 patients with advanced HIV infection followed up at Memorial Sloan-Kettering Cancer Center, New York, NY, from April 1, 1990, through December 31, 1990. RESULTS Fever occurred in 46% of patients. A diagnosis was made in 83% of episodes, with acquired immunodeficiency virus-defining illnesses accounting for half of the diagnosed cases. Patients whose conditions required more than 2 weeks to diagnose most often had lymphoma, Mycobacterium avium-intracellulare bacteremia, or Pneumocystis carinii pneumonia. Four patients had persistent unexplained fever without a clear source. Only one patient had fever that clearly responded to antiretroviral therapy. CONCLUSIONS Fever is common among outpatients with advanced HIV infection. Human immunodeficiency virus itself is rarely the cause of fever in such patients; the cause of the fever should be thoroughly evaluated.