BACKGROUND Alterations in blood-brain barrier permeability have been proposed to represent a relevant factor contributing to Parkinson's disease progression. However, few studies have addressed this issue in patients at different stages of disease. METHODS Albumin was measured in cerebrospinal fluid and serum samples obtained from 73 non-demented subjects with idiopathic Parkinson's disease and 47 age-matched control subjects. The albumin ratio (AR) was calculated to assess blood-cerebrospinal fluid and blood-brain barrier function. The group of patients with Parkinson's disease included 46 subjects with Hoehn-Yahr staging between 1 and 2 and 27, with a score ranging from 2.5 to 4. RESULTS Statistically significant differences in albumin ratio were found between patients with advanced disease, and both early-stage and unaffected groups. Conversely, early-phase patients did not differ from healthy subjects. Additionally, dopaminergic treatment seems to exert a possible effect on AR values. CONCLUSIONS Our study demonstrates that possible dysfunction of the blood-cerebrospinal fluid barrier, blood-brain barrier, or both, characterize Parkinson's disease progression. The associations between clinical scores, treatments and biochemical findings suggest a progressive impairment of barrier integrity during the course of the disease.