Gelsolin, an 82 kDa actin-binding protein, has potent acUn filament-severing activity in vitro. To investigate the in vivo function of gelsolin, transgenic gelsolinnull (Gsn-) mice were generated and found to have normal embryonic development and longevity. However, platelet shape changes are decreased in Gsn-mice, causing prolonged bleeding times. Neutrophil migration in vivo into peritoneal exudates and in vitro is delayed. Gsn-dermal fibroblasts have excessive actin stress fibers and migrate more slowly than wildtype fibroblasts, but have increased contractility in vitro. These observations establish the requirement of gelsolin for rapid motile responses in cell types involved in stress responses such as hemostasis, inflammation, and wound healing. Neither gelsolin nor other proteins with similar actin filament-severing activity are expressed in early embryonic cells, indicating that this mechanism of actin filament dynamics is not essential for motility during early embryogenesis.