Prostaglandins (PGs) have been suggested as mediators of bone resorption. In addition, their presence in the periodontal tissues has also been demonstrated. To characterize the involvement of PGs in orthodontic tooth movement, indomethacin, an aspirin-like drug and a potent inhibitor of PG synthesis, was administered orally to six mongrel cats; another group of six animals served as controls. These animals were fitted with orthodontic appliances that consisted of coil springs stretching between the right side maxillary and mandibular canines and third premolars. The data for tooth-movement measurements were analyzed by repeated measures factorial analysis of variance. At the end of the 21-day experimental period, the rate of tooth movement in experimental animals was approximately one half of controls (P less than 0.01). Findings of this study imply a significant role for PGs in bone resorption during orthodontic therapy. It is recommended that aspirin-like drugs not be administered to patients undergoing orthodontic tooth movement as it may extend the treatment time.