A prospective study was conducted to determine the etiology, clinical features, and outcome in a series of 32 consecutively enrolled HIV-infected patients with prolonged fever in whom high resolution (7.5 Mhz) sonography revealed multiple splenic microabscesses. Conventional (3.5 Mhz) sonography showed no splenic abnormalities in any patients. The diagnoses were: tuberculosis (14), visceral leishmaniasis (7), disseminated Mycobacterium avium complex infection (5), Salmonella spp. bacteremia (2), lymphoma (2), disseminated Rhodococcus equi infection (1), disseminated Candida krusei infection (1) and Pneumocystis carinii pneumonia (1). Twenty-eight patients were followed up for six months and four were lost to follow-up. In 16 patients with a clinical cure and microbiological eradication, the findings on follow-up high resolution sonography were normal, and in two patients the microabscesses persisted; ten patients died. In conclusion, the findings suggest splenic microabscesses may be a frequent condition in HIV-infected patients with prolonged fever, being an unspecific manifestation of the opportunistic diseases causing fever of unknown origin in this population. They cannot be detected by conventional abdominal sonography, whereas high resolution sonography is a useful technique for their detection and follow-up.