Treatment of mice with 0.01-1 μg of a synthetic serum thymic factor (FTS) significantly increased their resistance to lethal doses (1-5 × 10⁶ organisms) of Salmonella typhimurium LT2 (LT2). At least seven injections of FTS were necessary for induction of resistance, since the effects of one to three injections were variable. FTS additively potentiated the protective immunity to LT2 induced by immunization with an avirulent mutant of LT2, irrespective of the structural components of the cell wall lipopolysaccharides of the mutants, which are basically correlated with their immunogenicity and virulence. Activated macrophages may have a direct role in the induction of host resistance, since peritoneal macrophages from FTS-treated DBA/2 mice which are resistant to the doses of LT2 used could by themselves retard bacterial growth in vitro, whereas those from CBA/N mice which are relatively susceptible to LT2 did not inhibit bacterial growth without intervention of FTS-treated syngeneic T cells.