BACKGROUND The aim of the study was to describe the etiology and clinical characteristics of fever of uncertain origin (FUO) among HIV-infected patients. METHODS Prospective analysis of 35 episodes of FUO in HIV-infected patients from Balearic Islands that were studied through established guidelines. RESULTS Most patients were at advanced stages of HIV-1 infection (mean CD4 cell count, 60/mm3). Mean duration of fever until diagnosis was 57 days. Average time of hospitalization until etiological diagnosis of FUO was 26 days (range: 8-127 days). The cause of FUO was identified in 33 cases (94%). Tuberculosis accounted for 18 cases (51%) and visceral leishmaniasis for 8 cases (23%). Other opportunistic infections were the cause of FUO in 8 cases (17%). In one patient, fever was due to Kaposi's sarcoma. Two patients died while febrile, without and identified etiology. Four patients had more than one cause that could contribute to FUO. Imaging techniques that yielded more diagnostic information were abdominal ultrasonography and serial chest X-ray. Leishmania serology and tuberculin skin test showed a high specificity but low sensitivities. Invasive procedures with a highest diagnostic field were fine needle aspirate of lymph nodes, and liver biopsy. CONCLUSIONS FUO is more frequent in advanced stages of HIV disease. In our area, FUO is caused primarily by endemic opportunistic infections specially TB and visceral leishmaniasis, and rarely can be attributable to HIV or neoplastic diseases.