Chemically produced prostaglandin E1 (PGE1) was administered in clinical cases of orthodontic tooth movement. In the first phase, lingual arch springs were applied on both sides of the maxilla to upper first premolars which were scheduled for extraction. One side received submucosal injections of PGE1 and the other received vehicle injections. The rate of tooth movement in the buccal direction approximately doubled on the side of several PGE1 injections as compared to the control side. In the second phase, the PGE1 injections were applied in canine-retraction cases for up to 3 weeks in first-premolar-extraction cases. The rate of distal canine movement was almost double on the side receiving PGE1 injections as compared to the vehicle-injected side. In the third phase, the PGE1 injections were applied on routine canine retraction in first-premolar-extraction cases. The rate of distal canine movement was almost 1.6-fold on the side of PGE1 injections as compared to the vehicle-injected side. Throughout this study, no side effects were observed macroscopically in the gingiva and roentgenographically in the alveolar bone, except for a slight pain reaction consistent with orthodontic tooth movement.