Our laboratory is interested in the immunomodulation of porcine defense mechanisms against bacterial intracellular pathogens such as Salmonella typhimurium and S. choleraesuis. Past studies indicate that levels of serum tumor necrosis factor-a (TNF-a) increase after intranasal challenge with S. typhimurium but not after oral inoculation. Challenge with S. choleraesuis has no effect on serum TNF-a concentration in the blood, regardless of route. Route of inoculation with S. choleraesuis has been shown to affect levels of lymphocyte proliferation. Both oral and intranasal routes of inoculation stimulate peripheral blood B-cells while the intranasal route is more effective at stimulating peripheral blood T-cells. The inoculum dose of S. typhimurium or S. choleraesuis can also play an important role in the host immune response. TNF-a concentrations in the blood are much greater after a 106 S. typhimurium challenge than after a 104 S. typhimurium challenge. At high doses (;:o:l09 CFU) S. choleraesuis causes signs of lymphocyte suppression, which may affect the ability of the immune system to eliminate the bacteria. Pigs administered an intranasal dose of 108 CFU S. choleraesuis have similar immune responses as naturally infected animals.