We have characterized a murine model as an inexpensive, readily available and sensitive animal model for the evaluation of protective immune responses induced by various routes of administration of influenza A vaccine preparations. Using a non-mouse-adapted human influenza virus to infect unanaesthetized animals intranasally, we established that the optimum dose for infection of Balb/c mice was 104 plaque forming units of virus and that the optimum sampling time for measurement of virus yields in the organs of the respiratory tract was 72 h after challenge. We found that the infection was initiated in the nose and progressed by descending into the trachea and lungs over a period of days. Evaluation of protection against infection clearly showed that the tissues of the mouse respiratory tract were completely protected after administration of whole killed virus intranasally and partly protected when virus was administered subcutaneously. The protection correlated with the level of virus-specific IgA antibodies in saliva. © 1993.