This study compared the effects of local administrations of prostaglandin E-2 (PGE(2)) and 1,25-dihydroxycholecalciferol (1,25-DHCC) on orthodontic tooth movement in rats. Thirty-seven 6-week-old male Sprague-Dawley rats, weighing 160 +/- 10 g were used. Five rats served as the baseline control group. A fixed appliance system exerting 20 g of distally directed force was applied on the maxillary incisors of 32 animals for 9 days. Eight rats served as the appliance control group; 8 received a 20-muL injection of dimethyl sulfoxide (solvent for 1,25-DHCC) on days 0, 3, and 6; 8 received 20 muL of 10(-10) mol/L 1,25-DHCC on days 0, 3, and 6; 8 received a single injection of 0.1 mL of 0.1 mug PGE(2) only on day 0. There was no significant difference in tooth movement between the PGE(2) and the 1,25-DHCC groups. Both PGE(2) and 1,25-DHCC enhanced the amount of tooth movement significantly when compared with the control group. The numbers of Howship's lacunae and capillaries on the pressure side were significantly greater in the PGE(2) group than in the 1,25-DHCC group. On the other hand, the number of osteoblasts on the external surface of the alveolar bone on the pressure side was significantly greater in the 1,25-DHCC group than in the PGE(2) group. Thus, 1,25-DHCC was found to be more effective in modulating bone turnover during orthodontic tooth movement, because its effects on bone formation and bone resorption were well balanced.