Transgenic mice overexpressing the human amyloid precursor protein (APPV717F) develop cerebral amyloid angiopathy (CAA) as they age. We have examined the effect of CAA on blood vessels in vivo using multiphoton laser scanning microscopy. We are able to simultaneously detect, in an alive but anesthetized animal, fluorescent angiography of microvessels as well as the presence of amyloid angiopathy in 3-dimensional volumes near the surface of the brain. Analysis revealed dilation of the portions of vessels that were associated with amyloid deposition, even when that amyloid deposition was quite mild. In addition, analysis of the 3-dimensional reconstruction of the relationship between the vasculature and CAA suggest that CAA is initiated close to branch points of vessels. Taken together, these data suggest that CAA has a substantial effect on the physiology of the microvasculature in vivo.