This study evaluated periapical healing of induced apical lesions with concomitant loss of the buccal bone plate in a dog model using four foxhounds. In an initial surgery, pulp cavities of mandibular premolars were exposed to induce apical lesions. In the same session, the cortical bone covering the buccal root surfaces was surgically removed to simulate buccal bone loss. After radiographic confirmation of the development of apical lesions, sites were reentered for surgical treatment. Following apical and buccal debridement, root-end resection, and root-end filling, sites were subjected to three different treatment modalities: (1) flap readaptation (controls); (2) placement of a collagen membrane covering the apical defect and denuded root surface; or (3) placement of an anorganic bovine bone filler into the apical defect and onto the exposed buccal root surface, with additional application of a collagen membrane. Animals were sacrificed 7 months following the second surgery. Step sections were analyzed histometrically and morphometrically for periapical healing. Sites with membrane + filler showed a statistically significantly lower mean percentage of new bone formation within the former defect compared to both membrane-alone and control sites. No significant differences were found for tissue components deposited on the cut root face across treatment groups. Formation of a continuous thin layer of new cementum covering the exposed dentin surface and root-end filling material was a frequent finding. Analysis of the tissue regeneration on the buccal root aspect as well as the clinical periodontal parameters will be presented in a separate article.