The primary objectives of this double-blind, controlled clinical trial were to assess factor(s) which affect the success of guided tissue regeneration (GTR) procedures in mandibular Class II buccal furcation defects. Thirty subjects, with mandibular Class II furcation defects, were randomly assigned to one of two treatment groups; patients in Group A received oral hygiene instructions with scaling and root planing, while subjects in Group B received similar treatment but without subgingival scaling and root planing at the affected site. After initial oral hygiene instructions and scaling and root planing, GTR surgery was performed using ePTFE barrier membranes. Membranes were retrieved at 6 weeks and subjected to histological examination. Twelve months after regenerative therapy, clinical measurements and re-entry surgical measurements were repeated. Probing reduction (2.61 mm), horizontal probing attachment gain (2.59 mm), and vertical probing attachment gain (0.95 mm) were all significantly better compared to baseline. Likewise, significant improvements in furcation volume (8.0 microliters) and in bone measurements were observed at re-entry. There was no discernible difference between subjects for whom complete anti-infective therapy was deferred to the time of the surgery (Group B) compared to subjects in whom complete anti-infective therapy was performed as part of the hygienic phase of therapy (Group A). Pre-operative pocket depth was directly correlated with the magnitude of attachment gain as well as the amount of new bone formation in the furcation area. Subjects who maintained good oral hygiene and who had minimal gingival inflammation throughout the study demonstrated consistently better regenerative response.(ABSTRACT TRUNCATED AT 250 WORDS)