We evaluated the distribution of apolipoprotein E (apoE) immunoreactivity in mouse and human olfactory bulbs. ApoE immunoreactivity was present in the olfactory nerve and around the glomeruli. Immunoreactivity was seen in somata that appeared to be glial. No neuronal staining was seen. The apoE immunoreactivity was also present in the mouse olfactory bulb subependymal layer. The specificity of immunoreactivity was confirmed with apoE-deficient mice (apoE gene knock-out mice, apoE KO) which did not display any immunoreactivity. The presence of apoE around glomeruli and nerve suggest that apoE is associated with the continuous degeneration and regeneration processes that occur in the olfactory nerve. Experimental manipulation of the olfactory nerve may be a useful technique to determine the functions of apoE in a well-defined neural system.