The purpose of this study was to compare the amount and rate of tooth movement in young and mature rats administered 1,25(OH)2D3 simultaneous with application of mechanical force. In 30 seven-week-old and 30 28-week-old male Wistar rats, the right maxillary first molar was moved buccally with a fixed appliance. The appliances delivered forces ranging from 5 to 20 g. Twenty microL of 1,25(OH)2D3 (10(-10) and 10(-8) mol/L) was injected locally into the submucosal palatal area of the root bifurcation of the right first molar. The left side was injected with phosphate-buffered saline (PBS). In young rats receiving 10(-10) mol/L 1,25(OH)2D3 every three days, tooth movement significantly increased to 126% of that in PBS-injected control rats on day 20. In 1,25(OH)2D3-injected mature rats, tooth movement was stimulated markedly and increased with 10(-10) mol/L to 245% and with 10(-8) mol/L to 154% of the amount of tooth movement seen in the PBS-injected controls by the end of the experiment. PBS-injected rats had a plateau stage where tooth movement did not occur at all, while there was no such lag-time in the 1,25(OH)2D3-injected group which showed continuous tooth movement. The local injection of 1,25(OH)2D3 did not change serum calcium, phosphate, and alkaline phosphatase activity, and there were no apparent clinical or microscopic side-effects.