Arterial and arteriolar amyloid-β (Aβ) deposition in hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) and Alzheimer disease (AD) cerebral amyloid angiopathy (CAA) were studied as to morphology, extent, and association with mononuclear phagocyte system (MPS) cells using Aβ, a-smooth muscle actin, and monocyte/macrophage marker (HLA-DR, CD68, CD11c, CD45) immunohistochemistry. The HCHWA-D/AD arterial/arteriolar media showed compact Aβ deposits, first appearing at the media/adventitia junction, and concomitant smooth muscle loss. Only HCHWA-D CAA featured (a) severe involvement of larger arteries and (b) arterioles showing a single or double ring of radial Aβ surrounding compact Aβ. Radial Aβ appeared to develop at the media/adventitia junction. Monocyte/macrophage marker-positive foci/cells co-localized with HCHWA-D arterial Aβ. Focal HLA-DR/CD11c positivity was observed at the media/adventitia junction of AD/HCHWA-D arteries in the absence of local Aβ, but not in controls. Monocyte/macrophage marker positivity co-localizing with radial Aβ appeared continuous with perivascular cells and microglia clustering perivascularly. These results suggest that (a) MPS cells are topographically associated with HCHWA-D arterial Aβ and radial arteriolar Aβ, and (b) HLA-DR/CD11c immunoreactivity may appear at the media/adventitia junction prior to Aβ. The latter finding and the assumed formation of radial Aβ at the media/adventitia junction may relate to involvement of the abluminal basement membrane in CAA pathogenesis. The role of MPS cells in this process remains to be established.