One-hundred twenty root canals of dog teeth were cleaned, shaped, and obturated with gutta-percha and sealers using a lateral condensation technique. The sealers used were Sealapex, CRCS, and zinc oxide-eugenol. The animals were killed after 30 or 180 days and the specimens were examined histologically. Sealapex and CRCS caused a periapical tissue response similar to that found with the zinc oxide-eugenol. An ingrowth of connective tissue infiltrated with chronic inflammatory cells was noticed in cases where the filling material reached the apical stops. Regardless of sealer used, deposition of new hard tissue along the apical root canal walls was observed, which caused the partial closure of the apical opening. In the Sealapex and CRCS groups, sealer particles were found at a considerable distance from the apices. All overfilled specimens caused chronic inflammatory reactions in the periapical tissues.