The aim of our research is to determine the biological function of gamma delta lymphocytes and in particular the role they play in microbial immunity. Although evidence of gamma delta T-cell activation and expansion has been obtained from numerous infectious diseases, how they contribute to pathogen-induced immune responses is still not clear. Based upon extensive studies of gamma delta T-cell involvement in the immune response to viral and bacterial pathogens in both mice and humans, we have uncovered evidence of their direct involvement in terminating host immune responses to infection and preventing chronic disease. We have identified an interaction between peripheral gamma delta T cells and a population of activated, proinflammatory macrophages elicited by infection that occurs late in the course of infection during or after pathogen clearance. As a result of this interaction, activated gamma delta T cells acquire cytotoxic activity and kill the stimulatory macrophages, leading us to propose a model for gamma delta T-cell-macrophage interactions that contributes to macrophage homeostasis, the resolution of inflammatory immune responses, and prevention of chronic inflammatory disease.