The aims of this study were to evaluate the clinical and microbiological effects of initial periodontal therapy (IT) and to determine the additional effects of systemic amoxicillin (Flemoxin Solutab) 375 mg TID plus metronidazole 250 mg TID therapy, in patients with adult Actinobacillus actinomycetemcomitans (Aa)-associated periodontitis in conjunction with either Porphyromonas gingivalis (Pg), Bacteroides forsythus (Bf) and/or Prevotella intermedia (Pi). In addition the adverse effects of the antimicrobial therapy were also documented. A total of 22 patients were enrolled. The deepest, bleeding pocket in each quadrant was selected and at these 4 experimental sites clinical measurements and microbiological testing was carried out at baseline, after (IT), i.e., 21 weeks after baseline, and after antimicrobial therapy (AM), i.e., 35 weeks after baseline. At baseline, the mean plaque index (PI) amounted 0.5, 0.1 after IT and 0.3 after systemic AM. The mean bleeding index decreased from 1.6 to 1.2 after IT and a further decrease to 0.7 after AM was noted. Suppuration was completely eliminated after AM. The mean change of probing pocket depth (PPD) after IT amounted 1.4 mm and was further reduced with an additional mean change of 1.1 mm after medication. Clinical attachment gain was 1.1 mm after IT and an additional 0.9 mm was observed after AM. One of the 22 Aa positive patients and 4 of 17 Pg positive patients became negative for these species after IT. The number of patients with detectable Pi decreased from 16 to 10 after IT. After AM, in comparison to baseline, suppression below detection level for Aa was achieved in 19 out of 22, for Pg in 9 out of 17, for Bf in 13 out of 14, and for Pi in 11 out of 16 patients. By contrast, higher frequencies of Peptostreptococcus micros and Fusobacterium nucleatum were found after AM. On the basis of the microbiological results the study group was separated into 2 subgroups: group A consisted of subjects who had no detectable levels of Aa, Pg, Bf and <5% of Pi after AM. Group B consisted of those who still showed presence of one of these 3 species and/or > or =5% levels of Pi. After AM, group B had significantly higher PI, BI, PPD and CAL scores then group A. It is concluded that group A showed low plaque scores and no detectable periodontal pathogens. This microbiological condition has been associated with a long-term stable periodontium.