In this study ibuprofen (50.0 mg/kg, i.p.), rofecoxib (10.0 mg/kg, i.p.) and thalidomide (50.0 mg/kg, oral) were shown to prevent vincristine-induced mechanical hyperalgesia. Sprague-Dawley rats were injected every other day with vincristine (0.1 mg/kg) over 13 days. The animals were cotreated daily with vehicle (saline), ibuprofen, rofecoxib or thalidomide throughout the period of vincristine treatment. Mechanical withdrawal threshold to punctuate and radiant heat stimuli were determined prior to and then on alternate days throughout the treatment period. Vincristine vehicle-treated animals developed marked mechanical hyperalgesia from day 5 of chemotherapy and this lasted until the end of the experiment. Thermal thresholds were not altered by the administration of vincristine vehicle. Animals in the vincristine vehicle group neither gained nor lost weight during the treatment period. All three active drugs showed an antihyperalgesic effect on the responses to mechanical stimulation of the hind paw that was significant from day 5 for ibuprofen and thalidomide and from day 7 for rofecoxib. Thermal thresholds increased after the administration of both the NSAIDs and thalidomide. Rofecoxib was the only drug to show any beneficial effect in protecting the animals from failure to gain body weight.