Recent publications have shown that origin of tissue-resident macrophages varies with age (1). In the intestine, the first macrophages present at birth derived from embryonic precursors originate from yolk sac and fetal liver and express high levels of F4/80. These initial macrophages are progressively replaced around weaning by a CCR2–dependent influx of Ly6Chi blood monocytes by a process driven largely by the microbiota (2). In the present work we investigated the nature of the macrophage subsets present in the neonatal intestine at homeostasis and during a Cryptosporidium parvum infection in presence of conventional or reduced microbiota. C. parvum is a zoonotic protozoan that infects and completes its parasitic life cycle in the intestinal epithelial cells of the small intestine and affect primarily neonates. We previously demonstrated the importance of intestinal dendritic cells in the control of the infection by innate immune mechanisms (3) and decided to further explore changes in the macrophage subset composition during the infection with conventional and transgenic animals. One striking observation was the presence of a limited number of CD11c+CX3CR1int monocytes/macrophages in the neonatal intestine. However, these cells were strongly recruited (13-fold) during the infection while CD11c+CX3CR1hi cells were only modestly affected by the infection. The influence of the infection and of the bacterial flora on these neonatal macrophage subsets will be discussed.