Heat shock proteins (Hsps) have been regarded as cytoprotectants that protect brain cells from damage encountered following cerebral ischemia or during the progression of neurodegenerative diseases. In this study, we assessed the plasma Hsp70 and Hsp27 levels in not cognitively impaired (NCI) subjects and in patients with mild cognitive impairment (MCI), vascular mild cognitive impairment (VMCI), and probable Alzheimer's disease (AD). Comparison of the plasma Hsp70 and Hsp27 levels of the 4 groups revealed that only the plasma Hsp70 level of VMCI patients (14.11 ng/ml) was significantly higher than that of NCI subjects (11.32 ng/ml), MCI patients (10.16 ng/ml), and patients with probable AD (10.16 ng/ml) after adjustment of age, sex, and education (F=4.231, d.f.=3, p=0.008). Furthermore, there was no difference in plasma Hsp27 levels among the 4 groups. These findings suggest that the plasma Hsp70 level may be related to vascular factors or inflammation.