Polymorphic reticulosis (PMR) is a specific clinicopathological entity which commonly presents as an aggressive, necrotizing lesion of the upper airway. It is a separate nosologic entity from Wegener's granulomatosis, though its site and aggressive nature has lead to confusion in the distinction between these two different processes. Although radiotherapy has been acknowledged as the treatment of choice for limited upper airway PMR, little data exist to guide the radiation oncologist in the practical management of this disorder. We review our single institutional experience with PMR limited to the upper airway. Thirty-four patients (24 males, 10 females) with a median age of 44 years (range 19-80 years) are presented. Symptoms of nasal obstruction were present in 94%. Systemic symptoms such as fever, night sweats, and weight loss were noted in 62% and were often striking clinically. The nasal mucosa was most frequently involved (91%), although involvement of the paranasal sinuses (47%), palate (32%), as well as, other upper airway sites was not uncommon. Perforation of involved structures was recorded in 37%. All but 1 patient were treated with primary radiotherapy. Twelve relapsed with PMR and 3 additional patients manifested diffuse histiocytic lymphoma either within or adjacent to the original treatment field. The median survival relapse in these 15 patients was only 4 months, although 25% were salvaged at 5 years post-relapse. The overwhelming majority of relapses were noted within the first 3 years following treatment. An evaluation of radiotherapy parameters indicated that a minimum dose of 42 Gy or a TDF of 70 is necessary to achieve long-term local control. Pattern of failure analysis demonstrated in-field failure as the predominant failure site, and this problem should become much less significant with implementation of proper time-dose-fractionation schemes. Marginal failure was noted in 20% as a component of eventual failure sites suggesting the need for generous treatment volumes including clinically uninvolved adjacent structures at risk, such as palate, sinuses, and nasopharynx for nasal lesions. Finally, systemic failure occurred in 25%. Although this rate may be reduced by improved local treatment measures, ultimately effective systemic chemotherapy will be required to substantially impact on these patients' survival.