The association amoxicillin-clavulanic acid can be employed as an alternative to the usual antibiotic therapy of periodontitis. The purpose of this study was to determine subgingival microbial changes in 33 patients with periodontitis after using amoxicillin (500 mgrs.-t.i.d.) and clavulanic acid (125 mgrs.-t.i.d.) for 5 days. It resulted clinically in a decrease of both gingival index and plaque index (not significant) and microbiologically in absence of the main bacterial pathogens found pretreatment, such as Bacteroides melaninogenicus, Bacteroides intermedius, Eikenella corrodens and Actinomyces sp., although it was not able to eliminate Actinobacillus asinomycetemcomitans from a juvenile periodontitis and from a prepuberal periodontitis patient. Atibiotic susceptibility testing showed that all bacteria tested were sensitive to this antibiotic. Although this short term study shows good microbial response of main periodontal pathogens, long term studies are necessary to assess the effect of this antibiotic in periodontitis therapy.