The amount of sialic acid on the surface of the neutrophil influences its ability to interact with other cells. Neutrophil activation with various stimuli mobilizes intracellular sialidase to the plasma membrane where it cleaves sialic acid from cell surfaces. Since enhanced neutrophil adherence, spreading, deformability and motility each are associated with surface desialylation and critical to neutrophil diapedesis, we studied the role of sialic acid on neutrophil chemotaxis with interleukin-8 (IL-8), leukotriene B4 (LTB4), fMet-Leu-Phe (fMLP) and complement 5a in vitro. Migration of NANase-treated neutrophil across 3 μ pore size polycarbonate membranes was decreased in response to IL-8 and LTB4 but not to fMLP and complement 5a. These findings suggest that sialic acid content of receptors have a key role on chemoattractant-receptor binding and may be a novel strategy for limiting the inflammatory response.