The efficacy of oxyphenbutazone (OPB) in the control of postoperative inflammation was investigated, and previous findings were extended on the rate at which the inflammatory response of plasma seromucoids was significantly modified by this drug. Eighty - five surgical patients (hemorrhoidectomy, 39; vaginal hysterectomy, 23; tonsillectomy, 14; submucosal resection of nasal cavity, 9) were studied by the double-blind method. OPB was administered orally in a daily dosage of 400 mg. with a priming dose on the evening before surgery. Effective control of postsurgical inflammation was achieved in 34 of 46 treated subjects as compared with similar results in eight of 39 controls. Control of postoperative pain was pronounced when OPB was used. One patient developed an urticarial rash. Chemical studies were carried out in 65 surgical patients (39 treated with OPB; 26 controls). In the postoperative phase, mean plasma seromucoid values increased from presurgical levels by 39% in controls and by 13.9% in OPB-treated subjects. Hence, results of this clinical trial clearly demonstrate the usefulness of OPB in the control of postsurgical inflammation. Moreover, results of the chemical studies are in accordance with those previously obtained in animals.