When (p)ppGpp is absent, pathogenicity is compromised for reasons that vary with the organism studied. Deleting relA and spoT genes, but not relA alone, gave a (p)ppGpp state that resulted in strong attenuation in mice and noninvasiveness in vitro. Vaccine tests reveal that 30 days after single immunization with the (p)ppGpp strain, mice were protected from challenge with wild-type Salmonella at a dose 10-fold above the established LD.