Background. Despite improvements in locoregional treatment of stages III/IV squamous cell carcinoma of the head and neck (HNSCC), local and distant failure rates remain high. An effective adjuvant therapy is required for these patients. Among novel approaches is radioimmunotherapy, in which monoclonal antibodies (MAbs) are used for selective delivery of radiation to tumor cells. Methods. The suitability of 186Re-labeled chimeric MAb U36 (186Re-cMAb U36) for radioimmunotherapy was evaluated in a phase I study, with radiation dose escalating steps of 11, 27, and 41 mCi/m2. Tumor targeting was monitored with a gamma camera, and the maximum tolerated dose was established in 13 patients with recurrent or metastatic disease. Results. Administrations were well tolerated, and excellent targeting of tumor lesions was seen. Myelotoxicity was the only toxicity observed, resulting in dose-limiting toxicity in two patients treated with 41 mCi/m2. The MTD was established at 27 mCi/m2. A marked reduction in tumor size was observed in two patients, another showed stable disease for 6 months. Conclusions. Radioimmunotherapy with 186Re-cMAb U36 seems to be well tolerated, with bone marrow being the dose-limiting organ. The observation of antitumor effects is encouraging for further development of radioimmunotherapy for HNSCC.