Xerostomia (dry mouth), resulting from radiation damage to the parotid glands, is one of the most common and distressing side effects of head-and-neck cancer radiotherapy. A noninvasive, objective imaging method to assess parotid injury is lacking, but much needed in the clinic. Therefore, we investigated echo histograms to quantitatively evaluate the morphologic and microstructural integrity of the parotid glands. Six sonographic features were derived from the echo-intensity histograms to assess the echogenicity, homogeneity and heterogeneity of the parotid gland: (1) peak intensity value (Ipeak), (2) -3-dB intensity width (W3-dB), (3) the low (<50% Ipeak) intensity width (Wlow), (4) the high (>50% Ipeak) intensity width (Whigh), (5) the area of low intensity (Alow) and (6) the area of high intensity (Ahigh). In this pilot study, 12 post-radiotherapy patients and seven healthy volunteers were enrolled. Significant differences (p < 0.05) were observed in four sonographic features between 24 irradiated and 14 normal parotid glands. In summary, we developed a family of sonographic features derived from echo histograms and demonstrated the feasibility of quantitative evaluation of radiation-induced parotid-gland injury. © 2012 World Federation for Ultrasound in Medicine & Biology.