To evaluate the feasibility, maximum dose of drug tolerated, technical problems, systemic and local toxicity, response rate, overall and disease-free survival, we studied superselective intra-arterial infusion of high-dose carboplatin as part of a multimodality treatment for head and neck cancer. Forty patients with untreated stage II-IV head and neck squamous cell carcinomas received induction chemotherapy with high-dose carboplatin (three cycles at 2-week intervals using 300-350 mg/m2 per cycle), delivered via superselective transfemoral angiography followed by radiotherapy or surgery plus radiotherapy. No technical complications occurred during or after the infusion. Systemic toxicity was minimal, and local toxicity was moderate. At the end of chemotherapy the overall complete and partial response rate was 90% (36/40) at the primary site and 64% (16/25) at the neck nodes. The median follow-up was 24.4 months (range 3-52). To date 21 patients are alive without disease, 2 are alive with disease, 13 have died of disease, and 4 have developed a metachronous lung tumor. There was a good correlation between the response to chemotherapy and disease-free survival. No statistically significant benefit in survival was observed with respect to other series of head and neck tumors treated with different protocols. However, discriminating between responding and nonresponding patients, this procedure can have a prognostic significance in planning integrated treatments for these types of tumors.