Root canals of 49 teeth with necrotic pulp tissue in five monkeys were infected with Streptococcus faecalis ss liquefaciens, Actinomyces bovis, Fusobacterium nucleatum, Peptostreptococcus anaerobius, and Bacteroides oralis in various combinations. After 6 months the root canals and the periapical tissues were subjected to radiographic, bacteriologic, and histologic examinations. Signs of periapical inflammation were radiographically registered in 41 teeth, most frequently in teeth inoculated with a mixed flora. In 11 out of 16 teeth infected separately with Strep. faecalis ss liquefaciens, apical periodontitis was observed. Sera from the monkeys prior to and after the experimental inoculation were analyzed by means of gel diffusion, hemagglutination (HA), and complement binding test for antibodies against different antigen preparations of the homologous bacterial strains used for the inoculation. Detectable antibodies were seen with antigens of B. oralis in all five monkeys. Agglutinating antibodies were demonstrated with lipopolysaccharide-antigen of B. oralis in titers between 1:40 and 1:320. A marked reduction of the antibody level against lipopolysaccharide (LPS) antigen after mercaptoethanol treatment indicated that a main part of the antibodies registered was of IgM-class. The study shows that certain antigens of bacterial origin from infected root canals, while affecting the periapical tissues, also stimulate the production of circulating antibodies.