This study shows that neutrophils are critical for combating experimental systemic infections of mice by the bacterial pathogens Listeria monocytogenes, Salmonella typhimurium, and Yersinia enterocolitica. It shows that mice rendered neutropenic by treatment with the granulocyte-depleting monoclonal antibody RB6-8C5 are far more susceptible than immunocompetent mice to infection with each of these three pathogens. Compared to immunocompetent mice, neutropenic mice exhibit several defects in their antibacterial capabilities. Firstly, the immediate inactivation of Listeria, Salmonella, or Yersinia that initially implants in the livers and spleens that occurs in immunocompetent mice is abolished in these organs in neutropenic mice. Secondly, unlike immunocompetent mice, neutropenic mice neither control the subsequent proliferation of the inoculated bacteria in the livers and spleens nor prevent dissemination of infection to other organs. Thirdly, mice rendered neutropenic develop a generalized leukopenia in response to these three infections. Overall, this study indicates that neutrophils perform diverse antimicrobial functions that, combined, severely restrict the rate at which Listeria, Salmonella, and Yersinia multiply in the tissues during the preimmune phase of infection and thereby provide the host with the opportunity to develop and express more efficient specific protective immunity.