Bayou hantavirus, previously implicated in human hantavirus pulmonary syndrome in Louisiana, was isolated from a rice rat (Oryzomys palustris) captured in Georgia. The presence of antibody among rice rats captured throughout the southeastern United States and the extent of diversity among the genetic variants of Bayou viruses suggest that the rice rat is the most likely natural reservoir of the virus and that both virus and host have probably co-evolved for some years.