A substantial body of research has shown that Parkinson disease (PD) patients display an enlarged hyperechogenic substantia nigra (SN) by transcranial sonography (TCS). Nonetheless, the categorization of SN echogenicity is still subjective. A method is described to quantify SN echogenicity based on the gray-level histograms of digitized TCS images. In 31 PD patients and 57 controls, the gray-scale mean (GSM) of the SN, mesencephalon, and basal cisterns and their ratios were assessed using image-editing computer software. The GSM values were compared between the groups and correlated with age, SN area, and disease duration. The SN GSM was significantly higher in the PD group ( P < .05) with a positive correlation with age but not with disease duration. In this cohort of participants, mesencephalon echogenicity was found to increase with disease duration. These results would suggest quantitatively SN hyperechogenicity in PD. Quantifying SN echogenicity is feasible and might minimize subjectivity in PD diagnosis by TCS. The method has the potential to disclose subtle changes in other midbrain structures’ echogenicity engendered by the disease process as well.