Apolipoprotein E (apoE) is a known risk factor for Alzheimer's disease, but neither its roles in the pathogenesis nor its exact physiological functions in the brain is known. In order to study the apoE protein in the brains of normal mouse and transgenic mouse models of neurodegeneration, hamster monoclonal antibodies (MAbs) specific to mouse apoE were generated. N- and C-terminal fragments of mouse apoE protein were produced in E. coli as fusion proteins and used to immunize Armenian hamsters. Specificity of the antibodies was established by immunoblotting against sera and brain homogenates of wild type and apoE-deficient mice. MAb 884F11 was found most suitable for immunohistochemistry on 4% PFA-fixed brain tissues. The strongly positive structure in the normal brain was the astrocytes as identified by simultaneous staining for GFAP with lesser and regionally variable diffuse staining of the neuropil. GFAP-positive cells were variable in their content of apoE. ApoE immunoreactivity in the hippocampus and neocortex did not coincide with the tomato lectin binding, indicating that this apolipoprotein is not detectable in the microglial cells of the normal adult mouse brain.