The objective of this study was to compare the bone tissue reactions of Ketac-Fil to the most commonly used retrograde filling material, amalgam, in a rat model. Forty-eight Harlan rats were divided into three groups: amalgam, Ketac-Fil, and controls. Following anesthesia, the right lower incisor was extracted from each animal. A 3-mm long x 1-mm diameter polyethylene tube filled with amalgam or Ketac-Fil was implanted in the extraction site. The animals were killed at 14, 42, and 90 days; and the mandibles were dissected en block and processed histologically. The inflammatory reaction was assessed by the number of plasma cells, lymphocytes, polymorphonuclear neutrophils, giant cells, and osteoclasts within 100 microns of the implant. Bone formation was determined as either present or absent in the same area. There was no statistically significant bone apposition within 100 microns of the Ketac material, and there was a statistically significant increase in inflammation in the amalgam group. This study indicates that both Ketac-Fil and amalgam are relatively biocompatible, and provides support for clinical usage tests of Ketac-Fil as a retrograde filling material.