The International Committee of the Red Cross investigated an outbreak of fever of unknown origin in Ngozi prison, Burundi, which resulted in a crude mortality rate of 2.61% in January 1996. A definite diagnosis of epidemic typhus caused by Rickettsia prowazekii was established by enzyme-linked immunosorbent assay using specific antigens. Control measures included complete cleansing of the prison with cyfluthrine, shaving and dusting all prisoners with permethrin 0.5% dusting powder, and replacement of all mattresses and clothes. All prisoners and guards received a single dose of doxycyline (100 mg) simultaneously. The crude mortality rate dropped abruptly to 1.27% in February 1996 and remained at or below 0.5% from March onwards. Health authorities and medical agencies working in Burundi need to consider epidemic typhus in the differential diagnosis of fever of unknown origin in order to be able to take appropriate control measures in time.