ABSTRACTBackground.Human serum represents an important barrier to the entry of most mucosal organisms into tissues and to the systemic circulation. If at all present,Helicobacter pyloriwithin gastric tissue is rare, and bacteremia for this organism has been described only once.Methods.To assess the susceptibility ofH. pylorito the bactericidal activity present in normal human serum (NHS), we examined 13H. pyloriisolates. To assess the contributions of the classical and alternative complement pathways to killing, we added either C2‐deficient or factor B‐deficient serum, respectively, to heat‐inactivated NHS. Also we assessed the ability of the strains to bind125I‐C3.Results.After incubation for 60 minutes at 37°C, all 13H. pyloristrains were killed by NHS; heating to 56°C for 30 minutes ablated killing, indicating complement dependence for this phenomenon. In the absence of an antibody source, there was no killing when either an alternative or classical complement pathway source was used. Adding B‐deficient serum to heat‐inactivated normal human serum did not restore killing, but adding C2‐deficient serum permitted partial killing. All of the 13 strains bound125I‐C3. Although the kinetics varied from strain to strain, C3 bound was significantly correlated (r= 0.61,p= 0.03) with serum susceptibility.Conclusions.H. pyloriare susceptible to complement, alternative pathway activation appears critical, and C3 binding is a major loc