Lipoxins and 15-epimer lipoxins are generated during cell-cell interactions that occur during multicellular host response to inflammation, tissue injury, or host defense. Results to date indicate that they are present in vivo during human illness and carry predominantly counter-regulatory biological actions that lead to resolution of the inflammatory response or promotion of repair and wound healing. A selective receptor for lipoxin A4 has been identified by direct ligand binding, cloned, and characterized. Lipoxin and 15-epimer lipoxin analogs that resist metabolic inactiva-tion have been designed, synthesized, and shown in animal models to be lipoxin mimetics and novel antiinflammatory agents. These new investigational tools enable structure-function studies of lipoxin signal transduction, further elucidation of the role of lipoxins and 15-epimer lipoxins in host responses, and exploitation of their potent bioactions in the design of novel pharmacologic agents.