A number of dietary lectins have been shown to resist proteolytic digestion. These lectins interact with the small intestinal mucosa causing structural and functional changes. Concomitant to these changes, bacterial overgrowth was reported and a possible interaction between lectins and bacteria in the small intestine was postulated. The aim of this study was to investigate the effect of various lectins on adherence of Salmonella typhimurium to both isolated small intestinal enterocytes and ligated intestinal loops. Isolated intestinal cells or ligated intestinal loops were incubated with [3H] adenine-S. typhimurium in the presence or absence of concanavalin A, phytohemagglutinin, peanut agglutinin, and wheat germ agglutinin. Only concanavalin A promoted the adherence of various strains of nonfimbriated S. typhimurium to isolated viable intestinal cells. Other lectins showed no effect on the adherence. In situ studies showed that bacterial binding was increased in concanavalin A-treated intestinal loops, supporting the significance of the experiments in vitro. These data suggest that lectins may act by promoting bacterial adherence to the small intestine, thereby facilitating colonization and infection, and leading to bacterial overgrowth.