BACKGROUND To describe the clinical features and the final diagnosis of patients infected with human immunodeficiency virus who presented fever of unknown origin. METHODS Retrospective study, from November 1989 to January 1994, of all patients infected with HIV who had fever of unknown origin and who were admitted to a community hospital in a Mediterranean area in Alicante (Spain). Fever of unknown origin was defined as fever exceeding 38.3 degrees C lasting for at least three weeks with no diagnosis in the first three days of hospitalization after fulfilling clinical exam, three blood cultures, acid-fast bacilli stain in sputum and chest-X-ray. RESULTS Of a cohort of 231 patients, 27 (12%) were evaluated because of fever of unknown origin during their follow-up. Patients' mean age was 31 years (interval, 22-75) and intravenous drug use (81%) was the most common risk factor for HIV infection. A total of 31 episodes of fever of unknown origin were reviewed. Twenty-three (74%) episodes occurred in patients with less than 200 CD4 lymphocytes/mm3. A final diagnosis of fever of unknown origin was achieved in 24 (77%) episodes: visceral leishmaniasis (n = 11), tuberculosis (n = 9), non-Hodgkin's lymphoma (n = 1), CNS toxoplasmosis (n = 1), cryptococcal meningitis (n = 1) and drug adverse reaction (n = 1). CONCLUSIONS HIV-infected patients with fever of unknown origin very often show severe immunodeficiency. Cryptococcal antigen testing should be carried out in the initial evaluation of fever of unknown origin in HIV-infected patients. In our area, 64% of episodes of fever of unknown origin were caused by visceral leishmaniasis or tuberculosis.