Amorphorous and colorless spaces, Virchow-Robin spaces (VRS), were often found by HE stain around blood vessels in the edematous brain. Histochemical characteristic of the enlarged VRS caused by an advanced edema and detected by lectin stain using Griffonia simplicifolia I agglutinin in the brain stem, the occipital lobe and/or the cerebellum was examined by means of immunohistochemical method. After pretreatment with formic acid or proteinase K, formalin fixed-paraffin embedded tissue sections were incubated with antibodies (ABs) against plasma proteins such as amyloid P component, Ig G, albumin (Al), apolipoprotein E (Apo E), and lactotransferrin (Lf), and cellular proteins such as ubiquitin (Ubt), Tau-protein (Tau), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), CD68 (KP-1) and heparansulfate proteoglycan (HSG). The tissue sections were also incubated with antibodies against alanyl aminopeptidase-S (AAP-S) and alanyl aminopeptidase-N (AAP-N) without pretreatment. The VRS showed intensive reactivity with ABs against Amy P, AAP-S and AAP-N, moderate with ABs against Apo E and HSG, weak with ABs against Ig G, Al and Lf, feeble with ABs against Ubt, Tau and CD 68, and no with ABs against GFAP and MBP, respectively. Although the substances detected in VRS might be of blood plasma origin resulting from abnormalities in the blood-brain barrier, the mechanisms whereby the serum proteins and/or other substances are enriched in VRS remain incompletely understood.