This study was designed to investigate the carrier state of swine infected with Salmonella choleraesuis. Thirty-five pigs were divided into 3 groups. Groups 1 (n = 15) and 2 (n = 16) were challenged with 108 CFU of S. choleraesuis intranasally or by gastric route, respectively. Group 3 (n = 4) served as uninoculated controls. Pigs were necropsied at 2, 4, 6, and 12 weeks post inoculation. Clinical signs and microscopic lesions were more severe for group 1. Salmonella choleraesuis was recovered from a greater percentage of tissue samples for group 1 versus group 2 at 2, 4, and 6 weeks post inoculation. No differences were observed between groups at 12 weeks post inoculation. Regardless of route of inoculation, S. choleraesuis was most often recovered from the ileocolic junction, ileocolic lymph node, cecal contents, tonsil, lung and colon. Both groups shed S. choleraesuis in the feces sporadically throughout the 12 week period indicating that a carrier state is maintained for at least 12 weeks. However, group 1 shed higher numbers of S. choleraesuis initially. Serum IgG, IgM, and IgA antibody responses to S. choleraesuis lipopolysaccharide and heat extract antigens were observed for both groups. Higher serum IgG antibody titers to S. choleraesuis lipopolysaccharide were observed for group 2. Intestinal antibody responses for both groups included IgG and IgM responses but not an IgA response. Both routes of inoculation stimulated peripheral blood B-cells while the intranasal route (group 1) was more effective at stimulating peripheral blood T-cells. The reduction in levels of tissues infection and shedding observed for both groups coincided with the development of the host immune response. These data indicate that route of inoculation affects the development of humoral and cellular immunity, influences levels of Salmonella shed into the environment and the distribution of Salmonella within tissue.