It has been reported that decreased serum high density lipoprotein (HDL) cholesterol level is related with severity of Alzheimer's disease (AD). Here, 82 patients with AD and 40 non-demented individuals were examined to determine how the APOE-epsilon4 allele modifies plasma cholesterol fractions. In adjusting for age, sex and plasma albumin level, plasma HDL cholesterol level was inversely correlated with the APOE-epsilon4 dose only in the patients (P = 0.0048), while plasma low density lipoprotein (LDL) cholesterol level tended to be correlated with the APOE-epsilon4 dose in both groups, although this was not significant. The ratio of LDL to HDL cholesterol in the patients showed a similar correlation with the APOE-epsilon4 dose to that in the controls, and this correlation was evident (P = 0.0069) after putting all subjects into one group. However, neither HDL nor LDL cholesterol levels showed significant differences between the groups. These results indicated that the APOE-epsilon4 dose affects the composition of plasma cholesterol, and suggested that the genetic effect on plasma lipid metabolism could be distinctive in patients with AD.