Avirulent strains of Salmonella typhimurium are being considered as antigen delivery vectors. During its intracellular stage in the host, S. typhimurium resides within a membrane-bound compartment and is not an efficient inducer of class I–restricted immune responses. Viral epitopes were successfully delivered to the host-cell cytosol by using the type III protein secretion system ofS. typhimurium. This resulted in class I–restricted immune responses that protected vaccinated animals against lethal infection. This approach may allow the efficient use of S. typhimuriumas an antigen delivery system to control infections by pathogens that require this type of immune response for protection.