We measured the activities of choline acetyltransferase (ChAT) in the post mortem frontal cortex in 32 Alzheimer's disease (AD) patients with different apolipoprotein E (apoE) genotypes. The ChAT values were significantly lower for the AD patients with 2 epsilon 4 alleles than for those with 0 epsilon 4 (ANOVA, P < 0.05). The ChAT activities of AD patients carrying 2 or 1 epsilon 4 alleles and those without the epsilon 4 allele also differed significantly: 16.3 +/- 15.2 versus 30.5 +/- 20.6 pmol/mg protein per min, ANOVA, P < 0.05. However, the AD patients carrying the epsilon 4 allele were significantly younger than those with 0 epsilon 4 allele. The study indicates that AD patients carrying the epsilon 4 allele have a more severe cholinergic deficit than the AD patients without the epsilon 4 allele.