CXC chemokines have been implicated in the recruitment of neutrophils to sites of infection. To determine the role of CXC chemokines in the host response to urinary tract infection (UTI), female mice were treated with an antibody against the major CXC chemokine receptor in the mouse, CXCR2, before intravesical inoculation with Escherichia coli. Anti-CXCR2 prevented the influx of neutrophils in urine and kidneys. The absence of a neutrophil response only temporarily impaired the clearance of bacteria from the urinary tract, as indicated by 100- and 1000-fold more E. coli colony-forming units in urine and kidneys of anti-CXCR2-treated mice at 24 h, but not at 48 h, after the infection. UTI induced increases in the renal concentrations of the CXCR2 ligands macrophage inflammatory protein-2 and KC, which were not influenced by anti-CXCR2 administration. CXC chemokines play an important role in the development of a local inflammatory response to UTI.