In this study, we evaluated the microbiological and clinical effects of mechanical debridement in combination with metronidazole and amoxicillin therapy in 48 patients with Actinobacillus actinomycetemcomitans-associated periodontitis, 3 months and at least 24 months after active treatment. The results of this study showed that 47 out of 48 patients were still negative for A. actinomycetemcomitans subgingivally, at the mucous membranes, the tonsillar area and in the saliva, 2 years after therapy. The clinical results showed that a reduction of probing pocket depth, probing attachment level, bleeding index and plaque index was not only seen in the time between baseline and 3 months after therapy, but further clinical improvement was observed between 3 and 24 months after active treatment. We conclude that combined mechanical debridement and metronidazole plus amoxicillin therapy is very effective in suppressing A. actinomycetemcomitans below cultivable levels over a long period of time, suggesting elimination of this organism, and that recolonization of A. actinomycetemcomitans seems to be a rare event. The elimination of A. actinomycetemcomitans is paralleled by a further improvement of the periodontal status of the patients, even up to 24 months after active treatment.