Some gastrointestinal bacteria synthesize hydrogen (H(2)) by fermentation. Despite the presence of bactericidal factors in human saliva, a large number of bacteria also live in the oral cavity. It has never been shown that oral bacteria also produce H(2) or what role H(2) might play in the oral cavity. It was found that a significant amount of H(2) is synthesized in the oral cavity of healthy human subjects, and that its generation is enhanced by the presence of glucose but inhibited by either teeth brushing or sterilization with povidone iodine. These observations suggest the presence of H(2)-generating bacteria in the oral cavity. The screening of commensal bacteria in the oral cavity revealed that a variety of anaerobic bacteria generate H(2). Among them, Klebsiella pneumoniae (K. pneumoniae) generated significantly large amounts of H(2) in the presence of glucose. Biochemical analysis revealed that various proteins in K. pneumoniae are carbonylated under standard culture conditions, and that oxidative stress induced by the presence of Fe(++) and H(2)O(2) increases the number of carbonylated proteins, particularly when their hydrogenase activity is inhibited by KCN. Inhibition of H(2) generation markedly suppresses the growth of K. pneumoniae. These observations suggest that H(2) generation and/or the reduction of oxidative stress is important for the survival and growth of K. pneumoniae in the oral cavity.