The spleen is an important organ for the host response to systemic bacterial infections. Many cell types and cell surface receptors have been shown to play role in the capture and control of bacteria, yet these are often studied individually and a coherent picture has yet to emerge of how various phagocytes collaborate to control bacterial infection. We analyzed the cellular distribution of Listeria monocytogenes (LM) in situ during the early phase of infection. Using an immunohistochemistry approach, five distinct phagocyte populations contained LM after i.v. challenge and accounted for roughly all bacterial signal in tissue sections. Our analysis showed that LM was initially captured by a wide range of phagocytes in the marginal zone, where the growth of LM appeared to be controlled. The cellular distribution of LM within phagocyte populations changed rapidly during the first few hours, decreasing in marginal zone macrophages and transiently increasing in CD11c(+) DC. After 4-6 h LM was transported to the periarteriolar lymphoid sheath where the infective foci developed and LM grew exponentially.