A late phase II clinical study of 254-S, a new anticancer platinum complex, for head and neck cancer was conducted by the 254-S Head and Neck Cancer Study Group consisting of 31 institutions. As in the early phase II study for head and neck cancers, 254-S was administered at 100 mg/m2 by 60 min intravenous drip infusion, repeated at least twice at 4-week intervals. Of 80 cases registered, 66 were regarded as complete cases evaluable for tumor response. Complete response (CR) was observed in 7 patients (10.6%), partial response (PR) in 22 (33.3%), no change (NC) in 24 and progressive disease (PD) in 13, for a 43.9% response rate. Two CR and 11 PR (37.1% response rate) were obtained in 35 patients with prior chemotherapy, including 2 CR and 7 PR (33.3% response rate) in 27 patients previously treated with cisplatin. Of 70 patients evaluable for toxicity, side effects were observed in 60 patients (85.7%). Major toxic effects were hematotoxicity, including leukopenia (62.9%), thrombocytopenia (40.0%) and anemia (45.7%), gastrointestinal toxicity, including nausea and vomiting (64.3%), and anorexia (47.1%); grade 3 or 4 thrombocytopenia was found in 20.0% of the patients, and this toxicity was regarded as the dose limiting factor. Nephrotoxicity observed was mild and infrequent. Based on these results, it was concluded that 254-S is a very useful anticancer agent for the treatment of head and neck cancer.