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Tonate virus, subtype IIIB of the Venezuelan equine encephalitis (VEE) complex, was first isolated in 1973 in French Guiana, South America. However, very little is known about its pathogenicity; it was considered to be responsible for only mild dengue-like syndromes. In 1998, a 2-month-old boy living along the Oyapock river in French Guiana was hospitalized for fever and generalized status myoclonus, and despite treatment the patient died 72 h after admission. Testing showed the presence of IgM specific for viruses of the VEE complex. A sensitive seminested polymerase chain reaction derived from a previous study was developed to detect viruses from the VEE complex, since no virus could be recovered from clinical specimens cultured on mosquito cells or from intracerebral inoculation into newborn mice. The genome of a virus from the VEE complex was detected in postmortem brain biopsies, and Tonate virus was identified by direct sequencing. This is the first reported case of human encephalitis due to Tonate virus.