The present study compared the effectiveness of two antimicrobials, tetracycline and metronidazole, in reducing subgingiyal microorganisms in periodontal pockets using an ethyl cellulose strip as the delivery medium. The study involved 30 patients, with a minimum of 3 periodontal pockets with probing depths > 6 mm throughout the oral cavity. Patients were given supragingival scaling and then divided into 5 groups, depending on the length of time the medication was in place. Sites were marked for tetracycline, metronidazole, and placebo. Sites were wiped and isolated, and baseline microbiology samples were taken for Gram staining and culture methods. After treatment, subgingival microbiological samples were taken again. The ethyl cellulose strips were removed and analyzed for any remaining drug. Results showed that tetracycline and metronidazole can both be applied locally to periodontal sites using ethyl cellulose strips and markedly suppress the subgingival bacteria over a period of several days. The tetracycline showed a faster release; however, the metronidazole required a lesser concentration to achieve complete reduction of the subgingival flora. J Periodontol 1998;69:409–413.