A comparative study which evaluated two treatment modalities for regeneration of interproximal periodontal lesions was conducted. Eleven pairs of advanced periodontal lesions in 11 human subjects (6 male and 5 female) were treated in a split mouth design with expanded polytetrafluoroethylene (ePTFE) interproximal membranes alone (control) in one lesion and ePTFE interproximal membranes in combination with decalcified freeze-dried bone (test) in the other lesion. At 1 year post-treatment, both treatment modalities revealed a significant increase in clinical attachment levels from baseline (2.0 +/- 1.37 mm test, 2.0 +/- 0.88 mm control) with no significant differences between the two modalities. When the amount of new bone formed in these lesions was assessed using re-entry procedures, a significant difference in new bone formation from baseline was found only for lesions treated with ePTFE alone (0.4 +/- 0.78 mm test, 1.3 +/- 0.96 mm control). It was concluded that at 1 year post-treatment, significant clinical attachment gains could be obtained by the use of ePTFE barriers with or without DFDBA. Statistically significant results in bone fill were only found when ePTFE barriers were used alone.