Hyperechogenicity of the substantia nigra (SN) has been proposed to be a typical finding in Parkinson's disease (PD) and a marker of vulnerability to nigrostriatal dysfunction in healthy subjects. This large cross-sectional study including 1120 subjects older than 50 years without any signs of PD was performed to evaluate the association of SN hyperechogenicity and other proposed epidemiological risk factors for PD. Among all variables assessed only family history of PD and male gender proved to be significantly associated with SN hyperechogenicity, indicating a genetic predisposition for the ultrasound marker.