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Pulpitis, external root resorption, and pain may be experienced during orthodontic movement. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been suggested to control these changes. The purpose of this study was to observe pulp-dentinal reactions, root resorption, tooth pain, and tooth movement after the application of a 4-ounce intrusive orthodontic force to human maxillary first premolars in patients given the NSAID nabumetone. Thirty-four maxillary first premolars were evaluated. A placebo was prescribed to 17 patients after an intrusive force was activated and reactivated for an 8-week period on the right side. The same procedure was repeated on the left side after patients were given nabumetone. Pulp-dentinal reactions and external root resorption were evaluated by histology. Pain and movement were also evaluated. Nabumetone was found to be useful in reducing pulpitis, external root resorption, and pain caused by intrusive orthodontic movement, without altering tooth movement in response to the application of orthodontic force.