The long-term effects of varying concentrations and frequencies of injectable, exogenous prostaglandin E2 (PGE2) on the rate of tooth movement and the amount of root resorption were evaluated. There were 132 male Sprague-Dawley rats 8 weeks old that initially weighed 225 to 250 gm. Five animals were in a pilot study, while seven were baseline controls and eight were appliance controls. The remaining 112 animals were divided into two experimental time periods of 2 and 4 weeks. Then, each experimental time period was divided into four subgroups of 14 animals based on concentration levels of PGE2 injections, i.e., 0.1, 1.0, 5.0 and 10.0 micrograms. Half of these animals in the dosage subgroup received a single injection at appliance placement and the other half received weekly injections. A fixed orthodontic appliance consisting of closed-coil nickel-titanium springs were ligated between the maxillary incisors and maxillary first molars. The initial activating force was 60 gm. The results showed that injections of exogenous PGE2 over an extended period of time in rats did enhance the amount of orthodontic tooth movement. However, there was no statistically significant difference in tooth movement between the single and multiple injection groups or among the four concentration levels of PGE2 used in either the 2- or 4-week time periods. The amount of root resorption as seen from scanning electron micrographs did increase with the use of prostaglandin injections, specifically with increased numbers of injections and with increased concentrations of PGE2.