Many endogenous chemical mediators are known to orchestrate the host response controlling the inflammatory response which involves the recognition of self and nonself by leukocytes [1, 2]. These chemical mediators or ‘signals’ regu-late the traffic of leukocytes and the cardinal signs of inflammation. The classic eicosanoids such as prostaglandins and leukotrienes play key roles and exert a wide range of actions in responses of interest in host defense and inflammation (fig. 1)[3]. The scope and range of chemical mediators identified has, in recent years, expanded considerably [2] to include novel lipid mediators [4, 5], new cytokines and chemokines, gases such as nitric oxide and carbon monoxide [reviewed in 6, 7], and reactive oxygen species as well as new roles for nucleotides as mediators such as adenosine [8]. Among the most recent to be uncovered in this diverse class of compounds is inosine monophosphate, which downregulates neutrophil (PMN) trafficking [9](see http://serhan. bwh. harvard. edu). When generated in elevated levels as in human disease, many of these small molecules or chemical signals are thought to be ‘proinflammatory’, generated to promote and amplify inflammation. Uncontrolled, these compounds in excess are thought to lead to chronic inflammation (fig. 1).

Recent results from the author’s laboratory [7, 10, 11] and now from other laboratories indicate that endogenous lipid-derived mediators are generated to dampen the host response and orchestrate resolution [2, 12, 13]. The lipoxins (LX) were the first and defining members to be identified and recognized as endogenous anti-inflammatory lipid mediators of resolution [14](fig. 1). In this regard, these compounds can function as ‘braking signals’ for PMN and