M cells present in Peyer's patch tissue transport enteric antigens for presentation to underlying lymphoid tissue to initiate immune responses against intestinal infection. Present work investigates how interactions taking place between bacteria, epithelial cells, and immunocytes could contribute to initial detection and later elimination of enteric antigens. Oral infection of germ-free mice with Salmonella typhimurium aroA- caused a twofold to threefold increase in M cell numbers, crypt depth, and enterocyte migration rate after 7 days. These changes were accompanied by a twofold increase in follicle-associated epithelial tissue (FAE)-associated CD4+ and a threefold decrease in FAE-associated CD8+ counts. Salmonella also increased M-cell numbers shortly after infection. Other effects on crypt size and spleen weight took longer to develop. Salmonella probably creates M cells by changing the local subepithelial immune environment in the lymphoid follicle.