BACKGROUND: Tetracyclines have been extensively used as adjunctives to conventional periodontal therapy. Emergence of resistant strains, however, has been reported. This study evaluated longitudinally the tetracycline resistance patterns of the subgingival microbiota of periodontitis subjects treated with systemic or local tetracycline therapy+scaling and root planing (SRP). METHODS: Thirty chronic periodontitis patients were randomly assigned to three groups: SRP+500 mg of systemic tetracycline twice/day for 14 days; SRP alone and SRP+tetracycline fibers (Actsite) at four selected sites for 10 days. Subgingival plaque samples were obtained from four sites with probing pocket depths (PPD)> or =6 mm in each patient at baseline, 1 week, 3, 6 and 12 months post-therapy. Samples were dispersed and diluted in pre-reduced anaerobically sterilized Ringer's solution, plated on Trypticase Soy Agar (TSA)+5% blood with or without 4 microg/ml of tetracycline and incubated anaerobically for 10 days. The percentage of resistant microorganisms were determined and the isolates identified by DNA probes and the checkerboard method. Significance of differences among and within groups over time was sought using the Kruskal-Wallis and Friedman tests, respectively. RESULTS: The percentage of resistant microorganisms increased significantly at 1 week in the tetracycline groups, but dropped to baseline levels over time. The SRP+Actsite group presented the lowest proportions of resistant species at 6 and 12 months. No significant changes were observed in the SRP group. The predominant tetracycline-resistant species included Streptococcus spp., Veillonela parvula, Peptostreptococcus micros, Prevotella intermedia, Gemella morbillorum and Actinobacillus actinomycetemcomitans (Aa). A high percentage of sites with resistant Aa, Porphyromonas gingivalis and Tanerella forsythensis was observed in all groups at baseline. However, T. forsythensis was not detected in any group and P. gingivalis was not present in the SRP+Actsite group at 1 year post-therapy. Aa was still frequently detected in all groups after therapy. However, the greatest reduction was observed in the SRP+Actsite group. CONCLUSION: Local or systemically administered tetracycline results in transitory selection of subgingival species intrinsically resistant to this drug. Although the percentage of sites harboring periodontal pathogens resistant to tetracycline were quite elevated in this population, both therapies were effective in reducing their prevalence over time.