The role of bacterial lipopolysaccharides (LPS) has been evaluated for their influence on the human T cell-mediated anti-Salmonella typhiactivity. In nonendemic areas for salmonellosis this activity is exerted by CD4+lymphocytes armed by IgA, whereas in endemic zones besides these cells also CD8+lymphocytes armed by IgG display an elevated anti bacterial activity. These results suggest that, in endemic regions, continuous antigenic challenge and, in particular, that exerted by lipid A (the active moiety of LPS) may play a role in triggering this activity.In other series of experiments, pretreatment of endemic peripheral blood lymphocytes (PBL) with smooth and rough (Rb and Re) forms ofSalmonellaLPS leads to the inhibition of antibacterial activity. In this respect, Re-LPS, which contains lipid A covalently linked to the core-chetodeoxyoctonate, gives rise to the maximum of inhibition.Finally, fractionation of PBL by means ofS. minnesotaR345 (Rb) cytoadherence has led to the conclusion that anti bacterial activity is present in the Rb-unbound population, thus indicating that bacterial adherence to PBL is a distinct phenomenon from natural anti-S. typhiactivity.The overall results suggest that lipid A is able to modulate the expression of antibacterial activity exerted by human peripheral blood T cells.