The dissemination of a neurovirulent strain of influenza A/WSN (HON1) virus from infected lungs to brains of thymus-deficient nude and immunocompetent furred mice inoculated intranasally was compared. Nude mice were more susceptible to lethal disease following intranasal (i.n.) inoculation with A/WSN virus than furred mice based on the number of plaque-forming units (PFU) of virus required to constitute a median lethal dose (LD50). In normal mice, virus was cleared from the lungs of survivors and dissemination of virus from lung to brain was detected only rarely. Nude mice, in contrast, had frequent and early deaths with significant brain virus titers and histologic evidence of encephalitis. Adoptive immunization of recipient nude mice with suspensions of cytotoxic T-lymphocytes secondarily stimulated in vitro 24 h after i.n. challenge, reduced both brain virus titers and mortality in these animals. These data indicated that T-lymphocytes were a significant factor in preventing dissemination of neurotropic virus from lungs to the brains of infected mice.