The main objectives of this research project were to determine if the oral administration of certain novel innate (“natural”) immune enhancers would protect piglets against Salmonella infections and if the oral administration of these immune enhancers had beneficial effects on some important immune functions in young piglets. One immune stimulant, CpG DNA (CpG), is a component of bacterial DNA that is recognized by the pig’s immune system as a non-self threat and causes the pig to mount an immune response to the CpG DNA. By mounting a response to the CpG DNA, the pig’s immune system is also then primed to take on other pathogenic microbes that it may encounter, such as Salmonella. The other immune stimulant, flagellin (Flag), is a protein produced by bacteria and is a component of the bacteria’s flagella. Flagellin acts in much the same way as CpG on the pig’s immune system. Each of these innate immune stimulants are recognized by the pig’s immune system through members of a highly evolutionarily conserved family of receptors called the toll-like receptors (TLR). TLRs are now recognized as being highly important not only for initial encounters with most microbes, but are also important for the host to mount an acquired or “memory” response to pathogens during subsequent encounters.