Background Transcranial sonography is increasingly used to aid clinical diagnoses of movement disorders, for example, to identify an enlarged area of substantia nigra echogenicity in patients with Parkinson's disease. Objective The current study investigated characteristics of the midbrain at the anatomical plane for quantification of substantia nigra echogenicity. METHODS: Area of substantia nigra echogenicity, cross-sectional area of the midbrain, and interpeduncular angle were quantified in two groups of adults aged 18-50 years: 47 healthy non-drug-using controls (control group) and 22 individuals with a history of methamphetamine use (methamphetamine group), a cohort with a high prevalence of enlarged substantia nigra echogenicity and thus risk of Parkinson's disease. Results In the control group, cross-sectional area of the midbrain (4.47±0.44 cm.sup.2) and interpeduncular angle were unaffected by age, sex, or image acquisition side. In the methamphetamine group, cross-sectional midbrain area (4.72±0.60 cm.sup.2) and area of substantia nigra echogenicity were enlarged compared to the control group, and the enlargement was sex-dependent (larger in males than females). Whole midbrain area and interpeduncular angle were found to be weak predictors of area of substantia nigra echogenicity after accounting for group and sex. Conclusions History of methamphetamine use is associated with an enlarged midbrain and area of substantia nigra echogenicity, and the abnormality is more pronounced in males than females. Thus, males may be more susceptible to methamphetamine-induced changes to the brainstem, and risk of Parkinson's disease, than females.