We determined the frequency of cerebral amyloid angiopathy (CAA) in 135 consecutive cases of diffuse Lewy body disease (DLBD) (N = 67), Alzheimer's disease (AD) (N = 34), and normal elderly controls (NECs) (N = 34). DLBD cases were subdivided into those with pathologic changes compatible with coexistent AD (DLBD/AD) and those without sufficient AD-type changes to warrant that diagnosis. In each case, we assessed the frequency, severity, and distribution of CAA on multiple thioflavin-S-stained sections of cerebral cortex examined with fluorescent microscopy. Based on immunocytochemistry with beta-amyloid antibodies, amyloid in all the brains was composed of beta/A4. CAA was present in the leptomeningeal vessels in 50% of the NECs and in 100% of AD cases. In DLBD without coexisting AD, the frequency of leptomeningeal CAA was 58%, whereas in DLBD/AD, the frequency was 85%. The frequency of CAA in parenchymal vessels was 38% for NECs, 97% for AD, 43% for DLBD, and 85% for DLBD/AD. There was no significant difference in the frequency or severity of CAA between NECs and DLBD, but CAA was significantly more severe, and comparable with CAA in AD, in the cases of DLBD/AD. Ten NECs had focal CAA without senile plaques (SPs), whereas all other cases with CAA had at least some SPs. Neither CAA nor SPs were present in 14 cases, including seven NECs and seven DLBD cases. We found cerebrovascular accidents in 50 cases (including nine without CAA) and leukoencephalopathy in 24 cases. These results suggest that CAA and other AD-type changes are not concomitant with DLBD but are related to coexisting AD or pathologic aging.