The tyrosine kinase Syk plays an important role in multiple hematopoietic cell functions. To address the relevance of Syk for neutrophil function, the Arthus reaction - a model for an acute inflammatory response -was studied in wildtype mice reconstituted with Syk^-/-bone marrow. In these animals, neutrophil extravasation as well as inflammation-mediated edema formation and tissue damage were severely diminished when compared to control animals suggesting a role of Syk for neutrophil migration towards sites of lesion. Accordingly, we observed an enrichment of Syk at the lamellipodium of migrating neutrophil-like differentiated HL-60 (dHL-60) cells. Here, Syk co-localized with Vav, a guanine nucleotide exchange factor for Rac and Cdc42. The enrichment of Syk and Vav at the lamellipodium depended on Syk activity and its binding site for Vav. Time-lapse video microscopy revealed that murine Syk^-/-PMN and dHL-60 cells expressing a Syk kinase dead mutant or a Syk mutant lacking the binding site for Vav formed multiple unstable lamellipodia which severely compromised migration. These findings demonstrate a requirement of Syk for the acute inflammatory response in vivo by controlling neutrophil polarization and migration. Supported by DFG (WA 1048/2-1).