In mice administered Lactobacillus casei strain Shirota (LcS) intranasally, potent induction of interleukin 12, gamma interferon, and tumor necrosis factor alpha, which play a very important role in excluding influenza virus (IFV), was evident in mediastinal lymph node cells. In this model of upper respiratory IFV infection, the titers of virus in the nasal wash of mice inoculated with 200 g of LcS for three consecutive days (LcS 200 group) before infection were significantly (P < 0.01) lower than those of mice not inoculated with LcS (control group) (10 0.9 ؎ 0.6 versus 10 2.1 ؎ 1.0). The IFV titer was decreased to about 1/10 of the control level. Using this infection model with modifications, we investigated whether the survival rate of mice was increased by intranasal administration of LcS. The survival rate of the mice in the LcS 200 group was significantly (P < 0.05) greater than that of the mice in the control group (69% versus 15%). It seems that the decrease in the titer of virus in the upper respiratory tract to 1/10 of the control level was important in preventing death. These findings suggest that intranasal administration of LcS enhances cellular immunity in the respiratory tract and protects against influenza virus infection.Influenza virus (IFV) infections continue to be a significant public health problem for which improved therapies and preventive treatments are urgently needed. Some of the therapeutic approaches used thus far have included antiviral compounds (9, 23), vaccines (10), and biological response modifiers (2,8,21). In recent years, there has been an increased tendency in modern medicine to apply preventive treatments involving the use of probiotics, such as Lactobacillus or Bifidobacterium.A probiotic is defined by Havenaar (7) as a monoculture or mixed culture of living microorganisms that is applied to animals or man, beneficially affecting the host by improving the properties of the indigenous gastrointestinal microflora. It is restricted to products that contain living microorganisms, improve the health and well-being of man or animals, and can have an effect on all host mucosal surfaces, including the mouth, gastrointestinal tract (e.g., applied in food), upper respiratory tract (e.g., applied as an aerosol), or urogenital tract (local application). However, recently the definition of a probiotic has become even broader, and it has been concluded that dead bacteria and metabolic products with immunostimulatory activity or activity in prevention of infection by pathogens should be included in this category. Lactic acid bacteria and their products have been reported to have beneficial effects on host homeostasis and are effective in activating the immune system (4, 5).Lactobacillus casei strain Shirota (LcS), a member of the lactic acid bacteria, was originally isolated from the human intestine and has been used commercially for a long time to produce fermented milk. Various aspects of the effects of LcS have been studied intensively. LcS exhibits remarkable activity against syngen...