In October 2003, 9 human cases of hemorrhagic fever were reported in 3 provinces of Mauritania, West Africa. Test results showed acute Rift Valley fever virus (RVFV) infection, and a field investigation found recent circulation of RVFV with a prevalence rate of 25.5% (25/98) and 4 deaths among the 25 laboratory-confirmed case-patients. Immunoglobulin M against RVFV was found in 46% (25/54) of domestic animals. RVFV was also isolated from the mosquito species Culex poicilipes. Genetic comparison of virion segments indicated little variation among the strains isolated. However, phylogenetic studies clearly demonstrated that these strains belonged to the East-Central African lineage for all segments. To our knowledge, this is the first time viruses of this lineage have been observed in an outbreak in West Africa. Whether these strains were introduced or are endemic in West Africa remains to be determined.