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Notes: Background and aim: Several studies have reported adjunctive benefits to scaling and root planing (SRP) of systemic amoxycillin and metronidazole in the treatment of periodontal diseases. To date no comparisons have been made of these antimicrobials alone or in combination. The aim of this study was to compare the adjunctive benefits to SRP of amoxycillin and metronidazole alone and combined.Methods: 66 subjects 〈46 years of age with advanced chronic periodontal disease participated in this randomised, double blind, 4 parallel treatment group designed study. All subjects received quadrant SRP and then were prescribed amoxycillin capsules (250 mg) and metronidazole tablets (200 mg) (AM) or lactate capsules and metronidazole (PM) or amoxycillin and calcium lactate tablets (AP) or lactate and calcium lactate (PP). All medication was 3 of each per day for 7 days. Subgingival plaque samples were obtained and probing depth (PD), loss of attachment (LOA), bleeding on probing (BOP), suppuration (SUPP) and plaque (DEP) were recorded pre-treatment, 1, 3 and 6 months post-treatment.Results: Final group sizes were: AM=15, PM=16, AP=16 and PP=15. PD improved in all groups. Treatment effects were highly significantly different and always greatest in the AM and least in the PP groups. Benefits of PM and AP over PP were also noted. LOA improved in all groups and showed the same highly significant treatment differences, again favouring AM. BOP improved in all groups, particularly in AM compared to the other groups. SUPP improved in all groups and was virtually eradicated in AM with differences among treatments highly significant. DEP changed little in any group and there were no significant differences among groups. Microbiological data showed significant differences in favour of AM compared to PP and PM for total aerobes and anaerobes at 1 month. P. intermedia counts were always lower in active groups compared to PP and reached significance for AM and AP at 1 month and AM and PM at 3 months.Conclusion: The significant differences among treatment groups and the overall trend in the data, in line with other studies, support the considerable adjunctive benefits to SRP of amoxycillin and metronidazole combined in the treatment of advanced chronic periodontal disease.