Integrin ligation activates both cell adhesion and signal transduction, in part through reorganization of the actin cytoskeleton. Plastins (also known as fimbrins) are actin-crosslinking proteins of the cortical cytoskeleton present in all cells and conserved from yeast to mammals. Here we show that plastin-deficient polymorphonuclear neutrophils (PMN) are deficient in killing the bacterial pathogen Staphylococcus aureus in vivo and in vitro, despite normal phagocytosis. Like integrin β2-deficient PMN, plastin-deficient PMN cannot generate an adhesion-dependent respiratory burst, because of markedly diminished integrin-dependent syk activation. Unlike β2^–/– PMN, plastin-deficient PMN adhere and spread normally. Deficiency of plastin thus separates the classical integrin receptor functions of adhesion and spreading from intracellular signal transduction.