Orthodontic tooth movement in rats was examined by histochemical techniques for some enzymes associated with bone resorption and tissue damage. The maxillary first molar was moved buccally by means of a fixed appliance with predetermined forces for periods of from 10 hours to 6 days. The activities of acid phosphatase and lactate dehydrogenase were higher in cells in the connective tissue of the periodontal membrane (PDM) than in the oral mucosa. A low orthodontic force resulted in an initial redistribution of acid phosphatase-containing cells in the PDM followed by an increased activity of acid phosphatase. The activity of lactate dehydrogenase in the PDM was not affected by low orthodontic forces. The changes in distribution and activity of acid phosphatase and lactate dehydrogenase incident to a high orthodontic force were similar to those seen incident to a low force. However, there was one definite difference. A zone which lacked acid phosphatase activity and lactate dehydrogenase activity developed in the most compressed areas of the PDM. Prostaglandin synthetase activity was found exclusively in the bone marrow and seemed not to be affected by the orthodontic forces. However, some prostaglandin synthetase activity was found in the oral mucosa corresponding to the site of the orthodontic appliance. The adjacent bone surface was covered with cells showing an intense acid phosphatase activity. In the present study the magnitude of the orthodontic force seemed to be a determining factor for the vitality of the PDM but not for the tissue-degradation activity.