A relatively high incidence of infection by Actinobacillus actionomycetemcomitans can be shown in subgingival plaque samples obtained from patients with juvenile periodontitis. These organisms possess a potent leukotoxin(s) which rapidly destroys isolated human polymorphonuclear leukocytes (PMNs) and monocytes. If such leukotoxins operate in vivo, they could deprive the gingival crevice area of an essential antibacterial defense mechanism. We have found that sera from juvenile periodontitis patients consistently (greater than 90%) contain antibodies which neutralize Actinobacillus actinomycetemcomitans leukotoxin(s). On the other hand, sera from normal individuals or patients with other types of periodontal disease usually amplified rather than inhibited the leukotoxic reaction. Many patients with juvenile periodontitis have demonstrable defects in PMN or monocyte chemotaxis and this may place them at risk to gingival infection by Actinobacillus actinomycetemcomitans. The immune response against these organisms could be a crucial determinant in the course of juvenile periodontitis. While this disease is relatively rare, it does cause immeasurable emotional, physical and economic hardship for patients and their families. The identification of Actinobacillus actinomycetemcomitans as a potential pathogen in this disorder may eventually lead to specific forms of therapy to prevent and eliminate infection by this organism in these patients.