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Interferon-gamma (IFN-gamma) is a cytokine discovered by its ability to inhibit virus replication in cells. Although it exerts many different actions on different cells, the most prominent action is its macrophage activating effect. Macrophages, in turn, fulfill various regulatory and effector functions in inflammation. It can therefore be expected that interference with the action of IFN-gamma will affect inflammatory reactions. The studies reported here show that administration of neutralizing monoclonal antibodies directed against murine IFN-gamma modifies inflammatory reactions in various experimental models, in particular local LPS-induced inflammation in a footpad swelling model, LPS-induced lethal shock in a generalized Shwartzman type model, and experimental allergic encephalitis. These and other observations justify the hope that administration of monoclonal antibodies against IFN-gamma will be useful to treat or prevent certain inflammatory disorders.