The prognosis of patients with squamous cell carcinoma (SQC) of the head and neck (H&N) depends on the primary site and anatomical extent of the disease. Recurrence rates after conventional surgery (S) and/or radiotherapy (RT) remain low for localized tumors, whereas in advanced loco-regional disease they occur in over 60% of all cases. Several combinations of treatment modalities have been attempted in order to improve local control in Stages III and IV. Unfortunately, the recurrence rate remains high with added morbidity when conventional surgery is combined with pre or post-operative radiotherapy. Induction chemotherapy (CT) with Cisplatinum and Bleomycin has resulted in severe toxicities when combined with radiotherapy. To evaluate the toxicity of Carboplatin (CBDCA), a second generation platinum analog, when given simultaneously with conventional doses of radiotherapy, 26 patients with Stage IV SQC of the head and neck were treated at the University of Maryland Medical Systems. There were 23 males and 3 females; median age was 59 years and median Karnofski performance status was 60. Twenty patients had received no prior therapy; six had surgical exploration and excision with measurable residual disease. Anatomically, six patients had tumors of the oral cavity, twelve in the pharynx, one in the nasopharynx, four in the larynx, one in the hypopharynx, one in the maxillary antrum, and one was an unknown primary. These patients were treated as out-patients with weekly injections of Carboplatin. The dose was escalated: two patients received 60 mg/M2, seven received 75 mg/M2, thirteen were treated with 100 mg/M2, and four with 400 mg/M2. The radiotherapy was given daily with conventional fractions of 180 cGy and total tumor doses of 60-75 Gy. Toxicities were mainly hematological with median nadirs decreasing with increasing doses of Carboplatin. Mucositis was seen in over 80% of the patients, but interestingly enough, it has never been more severe than that observed with radiotherapy alone. So far, there has not been any kidney, ear, or neurotoxicities. Of 25 evaluable patients, 19 (76%) responded with 13 (52%) showing complete response. The overall median survival time is 266+ days (324+ for responders and 179+ for non-responders). The follow-up is still short, 10-14 months, but 9 of 13 patients with complete response have not yet progressed.