This study clinically evaluates the use of expanded polytetrafluoroethylene (ePTFE) membranes with or without the addition of decalcified freezedried bone allograft (DFDBA) in the treatment of interproximal intraosseous defects. 25 patients (26 paired defects) diagnosed with advanced periodontitis and having at least 2 bilateral interproximal probing depths of > or = 6 mm participated in the study. After the hygiene phase, measurements were made to determine soft tissue recession, pocket depth, and clinical attachment levels. Defects from each pair were randomly treated with either ePTFE alone (control), or ePTFE+DFDBA (experimental). Measurements were made during the surgery to determine crestal resorption, defect resolution and defect fill. Membranes were removed at 4 to 6 weeks. At 6 months, the soft and hard tissue measurements (surgical reentry) were repeated. Both groups showed statistically significant improvement when compared to baseline (p < 0.001), but no difference was determined between groups. Control sites showed a 50% bone fill and experimental sites had 54% bone fill. The defect resolution changes were also similar between control and experimental groups, respectively (80%, 74%). For this short-term study, it was concluded that either technique was beneficial for the treatment of intraosseous defects. Other studies are needed to assess the long-term stability of the improvements rendered by these treatments.