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ii Monocytes and macrophages express innate immune receptors such as FcγR and Toll-like receptor 4, which when engaged by their respective ligands; IgG immune complexes (ICs) and bacterial lipopolysaccharide (LPS), become activated to produce inflammatory mediators. While production of inflammatory mediators is critical for elimination of invading pathogens, this process must be tightly regulated to prevent collateral tissue damage. The goal of this thesis project is to analyze molecular mechanisms that regulate macrophage inflammatory responses to ICs and LPS. In the first part of this project we have analyzed the role of the inositol phosphatase SHIP-2 in FcγR-mediated macrophage responses and have established for the first time that SHIP-2 regulates these responses. During the course of these studies it was found that peripheral blood monocytes (PBM) express little to no SHIP-2. However, upon LPS treatment SHIP-2 expression is robust in PBM. A similar regulation of SHIP-1 was also found in PBM. These latter findings suggested a role for inositol phosphatase