The ε4 allele of apolipoprotein E (ApoE) is an important genetic risk factor for Alzheimer's disease (AD). Increasing evidence suggests that this association may be linked to the ability of ApoE to interact with the amyloid‐β (Aβ) peptide and influence its concentration and structure. To determine the effect of ApoE on Aβ and other AD pathology in vivo, we used APPsw transgenic mice and ApoE knockout (−/−) mice to generate APPsw animals that carried two (ApoE +/+), one (ApoE +/−), or no copies (ApoE −/−) of the normal mouse ApoE gene. At 12 months of age, Aβ deposition was present in the cortex and hippocampus and was also prominent within leptomeningeal and cortical blood vessels of all APPsw ApoE +/+ mice. Importantly, although Aβ deposition still occurred in APPsw ApoE −/− mice, no fibrillar Aβ deposits were detected in the brain parenchyma or cerebrovasculature. There was also no neuritic degeneration associated with Aβ deposition in the absence of ApoE. These data demonstrate that ApoE facilitates the formation of both neuritic and cerebrovascular plaques, which are pathological hallmarks of AD and cerebral amyloid angiopathy. Ann Neurol 2000;47:739–747