The aim of this study was to use clinical, radiographic and histological examinations to compare the dental pulp response in 162 premolar roots of eight dogs when trichloracetic acid (TCA), formocresol, mineral trioxide aggregate (MTA) and zinc oxide eugenol were used as pulpotomy agents. The teeth were divided into four groups. Following pulpotomy, the teeth were restored with amalgam. The animals were sacrificed at 48 h, 2, 4 and 8 weeks (two dogs at each interval). Histological evaluation indicated no cases with necrosis. After 8 weeks follow up, dentine bridge formation was evident in 20%, 50% and 91.7% of formocresol, TCA and MTA cases respectively. The first signs of bridge formation were seen for MTA at 2 weeks and for TCA at 4 weeks. MTA was superior to formocresol and TCA in treating pulps in dogs. However, bridge formation was seen in 50% of TCA cases after 8 weeks which is a desirable finding in pulpotomy procedures.