The purpose of this investigation was to study the microbiota associated with furcation-involved teeth before and after treatment by the guided tissue regeneration procedure (GTR) with non-resorbable ePTFE membranes, and to evaluate the benefit of additional systemic antimicrobial therapy (ornidazole). Each of 10 patients contributed 1 pair of bilateral mandibular molars with comparable furcation defects. 5 defects were treated with a membrane and the active drug, 5 were treated without a membrane but with the active drug, 5 were treated with a membrane and a placebo, and 5 were treated with neither a membrane nor the active drug. Considerable differences were found in the healing response of furcation defects treated with or without the antimicrobial agent. More horizontal attachment gain and increase in bone density was obtained in patients receiving the active drug than in patients receiving the placebo. With 1 exception, all sites with increasing horizontal probing depth were found in patients of the placebo group. Treatment with membrane plus ornidazole resulted in 0.7 mm mean recession and -1.2 mm mean decrease in horizontal probing depth. Sites treated with membranes generally tended to be positive for 15 target micro-organisms more often than sites treated without a membrane. This was particularly evident for Fusobacterium, Prevotella intermedia and Actinomyces odontolyticus. Whereas GTR-treated sites were often already positive upon removal of the membrane, re-emergence of target organisms seemed to be more delayed in the conventionally-treated sites.