Cotton rats (Sigmodon hispidus) were treated daily with corticosteroids and then inoculated with Keystone virus. Viremia and neutralizing antibody profiles were determined in treated and untreated rats. Compared to untreated rats, the treated rats were substantially more susceptible to infection, and their viremia lasted much longer. This experimental model suggests that stress associated with excess glucocorticoid synthesis within a natural population could cause an increase in transmission of arboviruses. It also suggests that the effects of stress should be considered when experimental laboratory studies are designed.