Effects of intranasal administration of influenza vaccine on persistent viral infection in gamma-ray irradiated mice were examined. BALB/c mice were exposed to a sub-lethal dose of gamma-ray (7Gy) and infected intranasally with non-lethal A/PR/8/34 (PR8, H1N1) viruses. The mice irradiated on days 0 or +2 of infection showed a significant weight loss with a slight decrease in survival rate 3 weeks after infection. These mice kept infective viruses in the nasal and/or lung sites even 3 weeks after infection (persistent viral infection) without IgA or IgG antibodies (Abs), although non-irradiated infected mice cleared the virus completely within 2 weeks. On the other hand, the pretreatment with the nasal adjuvant-combined vaccine (3 days before irradiation) prevented the persistent viral infection with the Abs. These results demonstrate that the exacerbation of influenza is induced by the irradiation during early days of infection (0-2 days) and that the exacerbation is prevented by the intranasal vaccination at least 3 days before irradiation.