Inflammation is a term used to describe a series of responses of vascularized tissues of the body to injury. The clinical signs of this phenomenon can now be related to increased flow in local blood vessels (calor and rubor), inн creased vascular permeability and/or cellular infiltration (tumor), and reн lease of a variety of materials at the site of inflammation that induce pain (dolor). Loss of function was later considered an additional cardinal sign of inflammation. However, mechanisms by which the function of a given vascularized tissue is impaired depend greatly on the nature of the tissue and on the detailed processes that contribute to the inflammatory reaction. The subject of this review is the mediators that produce these alterations. However, it is important to indicate at the outset that the inflammatory process is both varied and extremely complex. We emphasize the broad outlines of (a) alterations in hemodynamics and vessel permeability, and (b) infiltration by inflammatory cells as representing a common theme for the process. However, each site and stimulus may result in a different mix of these elements, a different time course, and a different outcome. The inflammatory process is also influenced by the nutritional and hormonal status of the individual, as well as by genetic factors. In addition, the processes themselves represent an extensive network of interacting mechaн nisms, mediators, and cells (85). This represents a high degree of redunн dancy in the system, which provides a mechanism both for amplification and for preservation of the response if one component of the system is deficient or inactivated. For example, we present an argument that biologiн cally active fragments of C5 are critical initiators of the acute inflammatory