This study shows that in mice selectively depleted of neutrophils by treatment with a monoclonal antibody, RB6-8C5, listeriosis is severely exacerbated in the liver, but not in the spleen or peritoneal cavity during the crucial first day of infection. At sites of infection in the livers of neutrophil-depleted mice, Listeria monocytogenes grew to large numbers inside hepatocytes. By contrast, in the livers of normal mice neutrophils rapidly accumulated at infectious foci and this was associated with the lysis of infected hepatocytes that served to abort infection in these permissive cells. In the spleen the situation was different, in that depletion of neutrophils did not result in appreciable exacerbation of infection. In this organ intact infected cells, many of which appeared to be fibroblast-like stromal cells, were found at foci of infection in the presence or absence of large numbers of neutrophils. This suggests that neutrophils are less effective at destroying L. monocytogenes-infected target cells in the spleen than in the liver. Consequently, at least during the first day, the organism remained free to multiply intracellularly in the spleen in cells that are permissive for its growth. Presumably, the same situation exists in the peritoneal cavity, because depleting neutrophils did not severely exacerbate infection initiated at this site.