Twenty-four healthy patients undergoing two separate operations for removal of an impacted third molar from one or the other side of the mandible, were included in a double-blind crossover study. On the two occasions either oxyphenbutazone (Tanderil) or placebo was given for 5 days, commencing on the day before surgery. Plasma analyses confirmed drug intake. A number of objective and subjective assessments were recorded for a paired comparison of the postoperative course, including swelling, trismus, local temperature and pain. On the 1st, 3rd and 5th postoperative days after the oxyphenbutazone-operation, the measured swelling averaged 86, 85 and 83%, respectively, of that after the placebo-operation; the corresponding P-values were less than or equal to 0.11, 0.03 and 0.06. Oxyphenbutazone did not significantly reduce the local hyperpyrexia. It exerted, however, an excellent pain relief, which may have contributed to less trismus and patient preference for the course with this drug. The results obtained with this model in humans showed considerable discrepancies with the analgesic and anti-inflammatory effects ascribed to oxyphenbutazone from results in animal models. Side effects were mild and infrequent, and no unfavorable effects on bleeding or wound healing were noted. Routine use of oxyphenbutazone in oral surgery, however, is not recommended.