Background: Convincing data exist that A. actinomycetemcomitans is an etiologic agent of periodontal disease. The purpose of this longitudinal study was to evaluate A. actinomycetemcomitans as a diagnostic indicator for periodontal disease in treated and periodontally maintained patients. Methods: Following comprehensive mechanical/surgical and supportive amoxicillin plus metronidazole therapy in 13 subjects with A. actinomycetemcomitans-associated destructive periodontal disease, we monitored subgingival A. actinomycetemcomitans at 4 individual sites in each patient up to 3 years post-therapy. The periodontal status was determined, and A. actinomycetemcomitans levels were quantitatively enumerated on TSBV agar in CFU/ml. Six patients with a persistence of subgingival A. actinomycetemcomitans at each reexamination within 3 years post-therapy were selected to be at risk for minor periodontal treatment outcomes and further recurrence of periodontal disease (test group). Seven subjects with a complete suppression of A. actinomycetemcomitans at each post-therapy visit served as controls. Results: The periodontal parameters decreased from overall values of 6.39 mm (probing depth, PD) and 7.64 mm (clinical attachment level, GAL) at the outset to 3.81 mm (PD) and 5.62 mm (CAL) 2 years post-therapy (Friedman, P less than or equal to0.05). At the 3-year reexamination, the PD/CAL scores increased to 4.03/5.78 mm. Among the 6 individuals (46%) with persistence of subgingival A. actinomycetemcomitans at the final 3-year visit (test group), periodontal status yielded increased levels of 4.45 mm (PD) and 6.60 mm (CAL). The control subjects (n = 7) revealed lower values of 3.67 mm (PD) and 5.09 mm (CAL). However, on a patient level, during the 3-year observational trial, the periodontal status of the 13 individuals was not statistically affected by subgingival infection with A. actinomycetemcomitans. Conclusions: Although in advanced periodontal disease, comprehensive mechanical and antimicrobial treatment is an appropriate regimen for sustained improvement of periodontal health, long-term control of subgingival infection with A. actinomycetemcomitans could not be achieved. In the maintenance care of destructive periodontitis, the persistence of A. actinomycetemcomitans is not a diagnostic parameter for periodontal disease.