The purpose of this investigation was to determine the histogenesis of periodontal regeneration using the principle of selective and guided cell repopulation of the root surface. A fenestration model, developed in the squirrel monkey, made it possible to exclude gingival epithelium and connective tissue and promote cell repopulation of the denuded root surface from the periodontal ligament and alveolar bone. Experimental and sham-operated control sites were compared histometrically after 3, 7, 14 and 35 days of healing. The results indicated that new cementum, bone and periodontal ligament formation occurred by the 14th day and that regeneration of the fenestration wound was almost complete by Day 35. Root resorption and ankylosis were observed in both experimental and sham-operated controls. There was significantly more periodontal regeneration in the experimental sites, which favored cell repopulation of the root surface from the periodontal ligament and alveolar bone.