The purpose of this study was to determine if adolescents and young adults with severe periodontal disease had precipitating serum antibody reactive with Actinobacillus actinomycetemcomitans, and, if so, to correlate presence or absence of the precipitin with clinical patterns of periodontal destruction. Double diffusion in gel was used to detect precipitins. Test and known positive standard sera were run in different wells against a common well containing a minute of sonicates from two strains of A. actinomycetemcomitans (Y4 and N27). Periodontal loss of attachment was measured with a probe on four surfaces per tooth; missing and unerupted teeth were noted with the aid of radiographs. Precipitating antibody was seen in 77% of sera from 22 subjects with localized juvenile periodontitis, 40% of 35 young subjects with more generalized severe disease, and 2% of 44 periodontally healthy individuals. About 80% of the positive reactions were with strain Y4. Within the diseased groups, there were significantly fewer involved teeth in subjects with precipitating antibody (Ab+) than among those in whose sera precipitins were not seen (Ab-). Comparisons of the distribution and severity of involved teeth between Ab+ and Ab- subjects were consistent with an hypothesis that high levels of antibody specific for A. actinomycetemcomitans have a protective effect against periodontal destruction.