Salmonella spp. are facultative intracellular bacteria which enter the body through the intestinal tract, We studied the roles of T cells expressing either the alpha and beta chains or the gamma and delta chains of the T-cell receptor (alpha beta T cells or gamma delta T cells, respectively) in the host defense against Salmonella using mice genetically deficient in tither alpha beta T cells, gamma delta T cells, or both T-cell subsets, These mutant strains of mice were infected orally or intraperitoneally with Salmonella dublin, and the progression of the disease was monitored by determining bacterial numbers in the feces, gut wall, Peyer's patches, mesenteric lymph nodes, spleen, and liver, Since susceptibility to Salmonella infection in mice is strongly affected by the alleles at the Ity locus, T-cell-mutant mice with either the Ity-sensitive or Ity-resistant phenotype were tested for resistance to S. dublin infection. We found that even though large numbers of intraepithelial and mucosal alpha beta and gamma delta T cells populate the normal intestine, they have no role in controlling the invasion of S. dublin into the intestine or the subsequent bacterial replication in the Peyer's patches or gut wall. Furthermore, systemic infections were equally severe for the first 6 days in normal, alpha beta T-cell-deficient, and gamma delta T-cell-deficient mice, and alpha beta but not gamma delta T cells were required for clearance of S. dublin, regardless of the Ity phenotype. However, mice that lacked both T-cell subsets had higher bacterial counts in their livers 15 to 18 days after infection than did cup T-cell-deficient mice, suggesting that gamma delta T cells can contribute to acquired immunity to S. dublin.