The objective of this study was to evaluate the application of an enamel matrix derivative (Emdogain) in deep periodontal pocket therapy. Twenty-one patients presenting intrabony and interproximal defects that could be treated with guided tissue regeneration were selected. The intrabony defects were divided into deep ( 9 mm) and very deep (>= 9 mm) defects. Bleeding on probing, Plaque Index, probing pocket depth, mobility index, gingival recession, probing attachment level, and surgical bone level were measured at baseline. At 12 months, cases were reexamined and indices recorded again. The mean probing depth decreased from 8.1 ± 2.1 mm to 3.2 ± 1.5 mm; attachment level decreased from 10.4 ± 2.4 mm to 7.0 ± 1.8 mm; recession increased from 2.3 ± 1.4 mm to 3.8 ± 1.8 mm; and surgical bone level decreased from 9.6 ± 1.9 mm to 7.1 ± 1.5 mm. No significant difference was noted between bone defects with one or 2 walls, between local and generalized periodontitis, or between smokers and nonsmokers. Significant statistical difference was found, however, between deep infrabony defects and very deep defects when attachment gain was considered. No adverse reaction to the substance was noted. The good clinical results obtained were not confirmed by radiologic results; standardized and computerized radiographs at 12 months did not reveal significant improvement. The histologic examination carried out on 2 samples did not show evidence of new attachment. Further studies are necessary to clarify the action mechanism and to evaluate the long-term results of this method.