APOLIPOPROTEIN E (ApoE) has been implicated in the pathogenesis of Alzheimer's disease (AD). ApoE is synthesized within the brain and has been suggested to be involved in the re-utilization of membrane lipids during neuronal repair and remyelination after injury. Spherical ApoE-containing lipoprotein particles are found in the cerebrospinal fluid (CSF). To study further the pathogenetic role of ApoE in degenerative brain disorders, we analysed ApoE in CSF. A significant (p < 0.001) reduction of CSF ApoE (1.5 ± 1.2 ng ml−1) was found in AD compared with controls (5.0 ± 2.7 ng ml−1). A less pronounced reduction was also found in frontal lobe dementia (3.1 ± 1.5 ng ml−1; p < 0.05). These findings support the hypothesis that ApoE is involved in the pathogenesis of degenerative brain disorders such as AD. An increased reutilization of ApoE-lipid complexes in the brain, as part of a generalized repair process, may explain the low CSF ApoE in AD. Alternatively, the reduction of CSF ApoE may be caused by absorption of ApoE to senile plaques and neurofibrillary tangles.