This study evaluated the efficacy of and investigated the site of action of aspirin and acetaminophen placed directly into tooth sockets after bilateral third molar surgery under local anaesthesia. On completion of surgery, 12 patients received in random, blind order either a suspension of aspirin in a methyl cellulose gel (100 mg/ml) in their tooth sockets and an oral placebo or the methyl cellulose alone in their sockets and an oral dose of aspirin (50 mg). The remaining 12 patients were treated in the same fashion with use acetaminophen. Patients were asked to record their pain, at intervals, over an 8-hour period on a 10 cm visual analog scale. Significantly less pain (p less than 0.05) was recorded throughout the 8-hour investigation period after both locally placed drugs than after placebo. There was no adverse effect on healing. The peripheral activity of aspirin is confirmed, and our findings suggest that acetaminophen has a significant peripheral effect in mediating its analgesic properties in postoperative pain after third molar surgery.