Experimental infection of chickens with controlled quantities of Salmonella typhimurium is often achieved by administration of a single oral inoculum of live bacteria to caged chickens. However, this method is a poor simulation of the natural process of S. typhimurium infection in the field, making the practical application of results obtained under such conditions tenuous. This experiment was designed to evaluate the use of horizontal transmission for the challenge/infection of chickens with S. typhimurium with the expectation that it may more closely resemble the natural situation and, therefore, the in-field physiological response of chickens. Further, the experiment allowed for comparison of both the kinetics and magnitude of the mucosal immune response following each mode of challenge by exposing the chickens to challenge by placing them on litter with S. typhimurium-infected seeder birds. Overall, birds challenged via seeded litter exhibited a slower rate of infection and a more gradual increase in serum antibody production compared with birds receiving a single oral inoculum.