Purpose: To investigate CT number (CTN) changes in gross tumor volume (GTV) and organ at risk (OAR) according to daily diagnostic-quality CT acquired during CT-guided intensity modulated radiation therapy for head and neck cancer (HNC) patients. Methods and Materials: Computed tomography scans acquired using a CT-on-rails during daily CT-guided intensity modulated radiation therapy for 15 patients with stage II to IVa squamous cell carcinoma of the head and neck were analyzed. The GTV, parotid glands, spinal cord, and nonspecified tissue were generated on each selected daily CT. The changes in CTN distributions and the mean and mode values were collected. Pearson analysis was used to assess the correlation between the CTN change, organ volume reduction, and delivered radiation dose. Results: Volume and CTN changes for GTV and parotid glands can be observed during radiation therapy delivery for HNC. The mean (+/- SD) CTNs in GTV and ipsi-and contralateral parotid glands were reduced by 6 +/- 10, 8 +/- 7, and 11 +/- 10 Hounsfield units, respectively, for all patients studied. The mean CTN changes in both spinal cord and nonspecified tissue were almost invisible (<2 Hounsfield units). For 2 patients studied, the absolute mean CTN changes in GTV and parotid glands were strongly correlated with the dose delivered (P<.001 and P<.05, respectively). For the correlation between CTN reductions and delivered isodose bins for parotid glands, the Pearson coefficient varied from -0.98 (P<.001) in regions with low-dose bins to 0.96 (P<.001) in high-dose bins and were patient specific. Conclusions: The CTN can be reduced in tumor and parotid glands during the course of radiation therapy for HNC. There was a fair correlation between CTN reduction and radiation doses for a subset of patients, whereas the correlation between CTN reductions and volume reductions in GTV and parotid glands were weak. More studies are needed to understand the mechanism for the radiation-induced CTN changes. (C) 2015 Elsevier Inc. All rights reserved.