Vitamin A deficiency results in multiple derangements that impair the response to infection. This review focuses on experimental models of specific virus infections and on cytokines and cells with cytolytic activity important to antiviral defenses. Altered specific antibody responses and greater epithelial damage in vitamin A-deficient hosts are consistent findings. The cytolytic activity of natural killer cells and various cytokine responses are altered. The inflammatory response to infection may also result in derangements in the transport and metabolism of retinol. We speculate that interaction of several factors may combine to explain the greater severity of infection seen in vitamin A-deficient animals and children. In addition to a preexisting lack of tissue vitamin A, these factors may include reduced mobilization and increased excretion of retinol during the acute phase response to infection, poor innate and specific immune response to virus, and delayed repair of damaged epithelia. Foci of vitamin A-deficient epithelia may be sites of penetration of bacteria and other agents, leading to secondary infections and contributing to an increased severity of infections and poor outcome in vitamin A-deficient animals and humans.