The recently completed VA Cooperative Study (CSP #268) of induction chemotherapy (cisplatin/5-FU) and definitive radiation (6600 to 7600 cGy) for organ preservation in advanced (stage III or IV) laryngeal cancer demonstrated that, although larynx preservation could be achieved in 64% of randomized preservation could be achieved in 64% of randomized patients, overall survival rates were not improved over conventional treatment (surgery/postoperative radiation). Of 166 patients randomized to induction chemotherapy, 46 had N2 or N3 disease and were analyzed to determine the effectiveness of the organ preservation treatment strategy on control of neck disease and survival. The clinical response of neck metastases to induction chemotherapy was significantly associated with subsequent salvage neck dissection (P = .008). The overall death rate was increased (P = .014) and survival time decreased in patients with less than a complete response in the neck after chemotherapy (P = .15). This was related primarily to failure to control the disease in the neck. The overall survival of patients achieving a complete response in the neck was improved over the randomized group of N2 or N3 patients treated with primary surgery. The findings suggest that response of neck nodes should be assessed independently of primary tumor response in trials of organ preservation strategies using induction chemotherapy, and that failure to achieve a clinical complete response in the neck warrants planned early salvage neck dissection in order to achieve improved overall survival.