C5a is a proinflammatory peptide generated through activation of the complement system, and is more potent than the other anaphylatoxins, C4a and C3a, in activating peripheral blood leukocytes. It can actively participate in the regulation of local cytokine network by stimulating production of proinflammatory cytokines. The proinflammatory effects of C5a are mediated through binding to a specific 7-TM chemoattractant receptor, C5aR (CD88). Binding of C5a to phagocyte C5aR induces chemotaxis, production of superoxide anions, and release of degradative enzymes. Pharmacologic or genetic disruption of C5a/C5aR interaction reduces sepsis, immune complex-induced lung disease, and Arthrogen-induced arthritis in experimental models.