OBJECTIVE: The majority of head and neck cancer (HNC) patients undergoing radiation experience xerostomia (dry mouth) which can range from mild to severe, even after completion of treatment. Its impact on quality of life (QoL) can be significant. The objective of this study was to evaluate the psychometric properties of a new questionnaire developed to assess the impact of xerostomia on QoL. METHODS: Data were obtained from radiation patients (RP) participating in the Evaluating Cytoprotection Health Outcomes (ECHO) Registry. ECHO, a prospective, longitudinal study of patients receiving amifostine prior to radiation and/or chemotherapy, collects clinical and outcomes information. All RP complete a questionnaire, including the Functional Assessment of Cancer Therapy-General (FACT-G) and a new questionnaire assessing xerostomia symptoms (XSQ) at baseline, 6-weeks (completion of radiation), and at 6 weeks, 3 months, and 6 months post treatment. RESULTS: A total of 104 with HNC, 43 with non-small cell lung cancer (NSCLC), and 38 with other cancer completed the questionnaire. The majority were male, Caucasian, and insured. Average age was 59 years old. Based on variable clustering, the XSQ produced three scales - Xerostomia Interference (9-items), Pain (5-items), and Nausea and Vomiting Symptoms (3-items). Overall, internal consistency was acceptable (Cronbach's alpha coefficients ranged from 0.81 - 0.96). Construct validity was demonstrated based on correlations between related items/scales. Known groups validity was upheld, as HNC patients reported statistically significantly lower scale scores (worse functioning) than NSCLC patients on all three domains (p <0.05). As expected, no statistically significant differences were reported between the groups on the FACT-G scales. CONCLUSIONS: The XSQ was found to be reliable and valid in this population and should be a useful tool for clinicians to monitor their patients. Responsiveness will be evaluated in the future. The ECHO Registry is currently ongoing. .