Arachnoid granulation is a protrusion of the arachnoid membrane into the cranial sinus, and is thought to play an essential role in the cerebrospinal fluid (CSF) absorption. Because the cells covering the apex region of the arachnoid granulation have different morphological features compared to the ordinary endothelial cells lining of the cranial sinus lumen, it has been expected these covering endothelial cells perform some specific function in the CSF absorption mechanism. However, little is known about functional differences between the covering endothelium of the arachnoid granulation and the ordinary sinus endothelium. In the present study, the characteristics of the covering cells located at the apex of arachnoid granulations of human, monkey and dog brain were examined by histochemical and immunohistochemical methods. The endothelial cells lining the cranial sinus lumen generally expressed such proteins as von Willebrand factor (vWF), CD31 and glycoproteins containing GS-1 or LE-1 lectin reacting sugar residue which are endothelial cell markers. However, the endothelial cells specifically located at the apex of arachnoid granulations failed to show vWF immunoreactivity, whereas the other endothelial markers were positive in each species we examined. Double staining of vWF antibody with other markers has clearly demonstrated that the endothelial cells on the apex region of arachnoid granulations exhibit no expression of vWF whereas cells lining the lateral region of arachnoid granulations and the luminal surface of ordinary cranial sinuses showed co-localization of these markers. The structural and histochemical differences between endothelial cells located at the apex region of arachnoid granulations and those of the sinus wall may reflect functional differences.