Intravenous administration of certain immunoglobulin preparations may cause severe adverse reactions, especially in hypogammaglobulinaemic patients. Because the exact mechanism of the adverse reactions is still unknown, we investigated the severe, prolonged hypotension induced in anaesthetized rats on rapid i.v. infusion of standard immunoglobulin preparations. The hypotensive response was previously shown to be associated with IgG aggregates in the preparations but independent of complement activation. We found that the hypotension could be prevented by treating the rats with a specific receptor antagonist of platelet-activating factor; or by depletion of the macrophages of the rats; or by pretreatment with monomeric IgG. This provided evidence that the hypotension is initiated by interaction of IgG-aggregates with Fc-receptors on macrophages, leading to the production of platelet-activating factor. We conclude that the rat model provides a sensitive and reproducible test system for macrophage-activating properties of immunoglobulin preparations for i.v. administration which may lead to vasoactive side effects.