During the past decade, our knowledge of Fc receptor interactions in inflammation has increased dramatically owing to the availability of single and multiple Fc-receptor-deficient mice. The deletion of activating Fc gamma receptors protects against inflammation in models of immune-complex-mediated diseases, whereas the deletion of inhibitory Fc gamma receptors triggers increased susceptibility to immune-complex-induced inflammation. These new insights have a profound impact on our understanding of inflammation in autoimmune diseases, such as systemic lupus erythematosus (SLE). Comprehending the complex interactions between activating and inhibitory Fc gamma receptors might lead to new therapeutic approaches for human diseases, including SLE.