We measured CSF acetylcholinesterase (AChE) activity in 57 Alzheimer's disease (AD) patients with different apolipoprotein E (apoE) genotypes at the early stage of the disease, and in 11 non-demented controls. The AChE activities of the whole AD group did not differ from those of controls. However, analysis of variance over the AD subgroups with two, one or no epsilon4 alleles and controls showed significant differences (p < 0.0001); the AD patients with two epsilon4 alleles had higher AChE activities than controls and AD patients with one or no epsilon4 and also the AD patients carrying one epsilon4 allele had higher AChE activities than the AD patients without the epsilon4 allele. The study suggests that cholinergic metabolism is altered in proportion to the number of apoE epsilon4 alleles. The different degree of AChE activity in relation to the number of epsilon4 alleles might have an impact on AD patients' responses to cholinesterase inhibitors.