Periodontitis appears to be an inflammatory response to a specific, albeit chronic, bacteriological infection associated primarily with the overgrowth of certain anaerobic organisms. These findings indicate that treatments aimed at controlling periodontitis should contain an antimicrobial component directed to the reduction, if not the elimination, of the periodontopathic organisms from the plaque. We have conducted 4 double-blind (DB) studies that have shown that the unsupervised usage of Metronidazole (MET) for 1 to 2 weeks plus scaling and root planing (S/RP), will reduce the need for periodontal surgery, increase attachment level, reduce probing depths, and reduce the levels and proportions of certain anaerobic organisms in the plaque, relative to a regimen consisting of the unsupervised usage of placebo plus S/RP. We have shown in the ongoing DB study, that Doxycycline (DOX) (a tetracycline analogue) will give results comparable to those obtained with MET. Antimicrobials used in this fashion will reduce the periodontal surgical needs by about 62% (DOX) to 76% (MET), compared to baseline values. Additional reduction of 10 to 15% can be obtained by placing ethylcellulose films containing MET or chlorhexidine (CHX) into pockets of teeth still requiring surgery after the systemic medication, thereby giving an overall reduction in surgical needs of about 90%. These results support the hypothesis that most advanced forms of periodontitis can be successfully treated by the combination of root surface debridement and short-term usage of systemic antimicrobial agents. We have in these DB studies, obtained answers to questions relating to who to treat? when to treat? how long to treat? how do you know that the treatment works? There remain unanswered, or still unaddressed, issues which we expect to answer with this competing renewal. We do not have enough data to determine which of the locally delivered agents is best. We do not know what the rate of reoccurrence of periodontitis will be in these patients 2 to 8 years following successful treatment. In the studies to be described we will determine the rate of recidivism of periodontitis following treatment with systemic and locally delivered antimicrobial agents. In particular, we will look for clinical and bacteriological predictors of relapse during the 2 to 8 years following the initial treatment. We will also determine, using a DB design, whether the delivery of antimicrobial agents via a slow release delivery system can achieve a reduction in surgical needs comparable to that which we have observed with systemic MET or DOX.