THIS REPORT DESCRIBES THE CLINICAL AND MICROBIOLOGICAL FEATURES Of 30 refractory patients and their response to a combined local and systemic therapy at 6 weeks and 3 years following treatment. The refractory treatment protocol (RefTx) consisted of a 2-week regimen of amoxicillin/clavulanate potassium in conjunction with professional, intrasulcular delivery of povidone iodine, and chlorhexide mouthwash rinses b.i.d. Eightyseven percent of the patients had favorable clinical responses to the RefTx and could be divided into 3 groups (A, B, C) based upon initial flora patterns and the shifts that occurred following treatment. Pretreatment prevalence of Porphyromonas gingivalis (P.g.) was 36.7%. The RefTx was effective in reducing P.g. below detection levels in 10 of the 11 positive patients at P <0.01; each of these 10 patients (Group A) demonstrated significant gain in attachment. Other black-pigmented Bacteroides species (OBP) were isolated from 70% of the patients at baseline. Nine of these patients did not harbor P.g., showed clinical improvement upon treatment, and were OBP negative following treatment (Group B). Group C patients (7) demonstrated clinical improvement with therapy and did not fit into either Group A or B based upon microbial patterns. Group D patients (4) did not show clinical improvement with 3 patients harboring either P.g. or OBP after treatment. The RefTx was effective at reducing probing pocket depth with a 56% decrease in the number of pockets greater than 6 mm at 6 weeks. This was accompanied by an overall gain of greater than or equal to 1 mm of probeable attachment in 45% of all sites. The clinical effects of the RefTx were shown to persist at 34.3 months with an apparent attachment gain of greater than or equal to 1 mm in 41.2% of sites. These data suggest that P.g. and OBP are important pathogens in refractory periodontitis and that the RefTx protocol is an acceptable, non-invasive alternative for the management of these patients.