Endodontic fillings were challenged with bacterial ingress in mandibular premolars of 4 beagle dogs. Groups 1, 2, and 3 (n = 9), had canals filled with gutta-percha and sealer, gutta-percha alone, and sealer alone, respectively. After 2 wk, pulp chambers were inoculated with plaque. Group 4 (n = 9) and group 5 (n = 5) had canals either filled as in groups 1 to 3 or unfilled, respectively, but not inoculated. Group 6 (n = 5) had canals unfilled and inoculated. Teeth were radiographed periodically for 14 wk, dogs terminated, and jaw blocks retrieved and processed for light microscopic examination. Rarefying osteitis appeared in group 6 at 3 wk and in groups 2, 3, and 5 at 11 wk. Periradicular inflammation was none, mild, or severe. Occurrence of severe inflammation in groups 1 to 6 was 0, 11%, 33%, 0, 60%, and 100%, respectively. Groups 1 to 3 combined differed significantly from group 4 (repeated-measures ANOVA, p < 0.05). This model could be used to assess the functional efficacy of endodontic fillings in vivo.