We examined the impact of vitamin A deficiency on the host response to an acute, viral infection of the respiratory tract by infecting BALB/c mice with a mouse-adapted strain of influenza A virus. Several indicators of the severity of infection were examined, including the rate of virus clearance from the lungs, the extent of inflammatory lesions, and percentage of survival. None of these was affected by vitamin A deficiency. Following the acute phase of infection, however, the regeneration of normal, respiratory epithelium was impaired and adenomatoid, metaplastic lesions developed within inflammatory foci in the lungs of deficient animals. The antibody response to infection was also characterized: the influenza A-specific immunoglobulin A (IgA) response in the respiratory tract was markedly decreased by vitamin A deficiency, but tracheal and lung lavage IgG titers were not affected. The serum IgM and IgG responses, and the serum hemagglutination-inhibition response, were also diminished by vitamin A deficiency. Decreased mucosal IgA titers and impaired regeneration of normal respiratory epithelium could impair recovery from a primary infection and increase susceptibility to opportunistic secondary infections.