La Crosse virus is a mosquito-borne arbovirus that causes encephalitis in children. Only nine cases were reported in Tennessee during the 33-year period from 1964-1996. We investigated a cluster of La Crosse encephalitis cases in eastern Tennessee in 1997. Medical records of all suspected cases of La Crosse virus infection at a pediatric referral hospital were reviewed, and surveillance was enhanced in the region. Previous unreported cases were identified by surveying 20 hospitals in the surrounding 16 counties. Mosquito eggs were collected from five sites. Ten cases of La Crosse encephalitis were serologically confirmed. None of the patients had been discharged from hospitals in the region with diagnosed La Crosse encephalitis in, he preceding 5 years. Aedes triseriatus and Aedes albopictus were collected at the case sites; none of the mosquitos had detectable La Crosse virus. This cluster may represent an extension of a recently identified endemic focus of La Crosse virus infection in West Virginia.