Bactericidal/permeability-increasing protein (BPI) from human polymorphonuclear neutrophils plays a major role in the host defensive response to gram-negative infections. This 50 kD cationic protein binds to the lipid A region of lipopolysaccharide (LPS) with high affinity, neutralizes the biological activities of LPS, and has potent bactericidal activity against a wide range of gram-negative bacteria. Because of these properties, BPI is under investigation as a novel clinical treatment for septic shock. Screening of more potential derivatives for multiple isomorphous replacement is currently in progress. Native data has been collected and appears to extend to 2.5 w resolution and is currently 40% complete.