SUMMARY: Yellow fever (YF), which is caused by a mosquito-borne virus, is an important viral hemorrhagic fever endemic in equatorial Africa and South America. Yellow fever virus (YFV) is the prototype of the family Flaviviridae and genus Flavivirus. The aim of this study was to determine the seroprevalence of YFV in selected health facilities in Western Kenya during the period 2010-2012. A total of 469 serum samples from febrile patients were tested for YFV antibodies using in-house IgM-capture ELISA, in-house indirect IgG ELISA, and 50z focus reduction neutralization test (FRNT 50 ). The present study did not identify any IgM ELISA-positive cases, indicating absence of recent YFV infection in the area. Twenty-eight samples (6z) tested positive for YFV IgG, because of either YFV vaccination or past exposure to various flaviviruses including YFV. Five cases were confirmed by FRNT 50 ; of these, 4 were either vaccination or natural infection during the YF outbreak in 1992-1993 or another period and 1 case was confirmed as a West Nile virus infection. Domestication and routine performance of arboviral differential diagnosis will help to address the phenomenon of pyrexia of unknown origin, contribute to arboviral research in developing countries, and enhance regular surveillance.Yellow fever (YF), a disease caused by mosquitoborne virus, is an important viral hemorrhagic fever endemic in equatorial Africa and South America (1,2). Yellow fever virus (YFV) is the prototype of the family Flaviviridae and genus Flavivirus (3). The genus Flavivirus contains approximately 70 viruses including YFV, dengue viruses (DENVs), Japanese encephalitis virus (JEV), and West Nile virus (WNV) that are of major human public health concern (4). An estimated annual incidence of 200,000 cases of YF causing 30,000 deaths is reported each affected individuals without treatment (4,5). In the eastern African region, YF outbreaks have been reported in Kenya (1992-1993) (6,7), South Sudan (2003, Uganda (2010-2011) (10), Sudan (2012) (11), and Ethiopia (2013) (12).YF cases are difficult to diagnose from the clinical symptoms in the early stages of the illness because of`n on-specific influenza-like symptoms'' that are similar to those of other febrile illnesses. Differential diagnoses may include malaria, viral hepatitis, dengue, leptospirosis, or other hemorrhagic fevers (13). WHO recommends case definition for suspected YF as``any case presenting with acute onset of fever, with jaundice appearing within 14 days after the onset of the first symptoms'' (14). The aim of this study was to determine the seroprevalence of YFV in selected health facilities in Western Kenya during the period 2010-2012.A total of 469 human whole blood samples were collected from the following healthcare facilities in Kenya: Andersen Medical Centre (AMC), Endebess Sub District Hospital (END), and Kitale District Hospital (KDH) in Trans Nzoia County; Centre for Infectious and Parasitic Diseases Control Research, Kenya Medical Research Institute (KEMRI) clinic (CIP) lo...