To characterize the clinical features of human immunodeficiency virus (HIV)-associated fever of unknown origin (FUO) in the United States, we performed a retrospective analysis of cases that fulfilled specific criteria (published by Durack and Street in 1991) at two medical centers in the United States between 1992 and 1997. Seventy cases met criteria for HIV-associated FUO; the mean CD4 cell count was 58/mm3, and the mean duration of fever was 42 days. A cause of FUO was found in 56 of the 70 cases; 43 were of a single etiology, and in 13 cases multiple conditions were established. The most common diagnoses were disseminated Mycobacterium avium infection (DMAC; 31%), Pneumocystis carinii pneumonia (13%), cytomegalovirus infection (11%), disseminated histoplasmosis (7%), and lymphoma (7%). In this United States series, FUO occurs most often in the late stage of HIV infection, individual cases often have multiple etiologies, and DMAC is the most common diagnosis.