The functional significance of zinc deficiency on primary and secondary host responses to infection with a facultative intracellular pathogen was studied in specific pathogen free rats. Groups of female rats fed either a low zinc or normal diet for 8 or 10 weeks were infected with Listeria monocytogenes five days prior to sacrifice. Zinc-deficient rats demonstrated thymic atrophy, reduced delayed hypersensitivity responses to listeria antigen, and impaired lymphocyte response of spleen cells to phytohemagglutinin, but not to Concanavalin A. Separate groups of zinc-deficient or control rats were vaccinated with viable L. monocytogenes 10 days prior to respiratory challenge. Vaccination resulted in successful control of bacteria in both dietary groups.