A prospective pilot study involving preoperative intraarterial chemotherapy with cisplatin in locally advanced oral and oropharyngeal carcinomas was initiated in March 1982. Twenty patients with TNM Stages III and IV disease underwent continuous intraarterial chemotherapy with cisplatin (90 mg/m2, at 1 mg/hour) and intravenous chemotherapy with methotrexate (50 mg/m2 X 1 dose). Arterial access was obtained by retrograde cannulation of the superficial temporal artery. One patient died of sepsis from leukopenia (mortality 5%). Catheter-related complications, most of them avoidable, totalled 30%. The total tumor response rate was 94%. With a median duration of follow-up of 14 months, the median survival of the group was not yet reached at 39 months. Eleven patients subsequently underwent definitive surgery and radiation with curative intent. When compared with matched historical controls, survival benefit was demonstrated: 60% versus 28% alive at 39 months (P = 0.015). Regional chemotherapy of cancers of the head and neck region is a feasible procedure with acceptable and avoidable morbidity. It should continue to be investigated in experimental protocols to improve patient survival.