Variation at the apolipoprotein E (APOE) gene locus has demonstrated a consistent impact on lipoprotein levels. APOE typing was performed for 488 healthy, caucasian, premenopausal women participating in the Women's Healthy Lifestyle Project (WHLP) aimed at reducing total fat, saturated fat and cholesterol intake and promoting physical activity. Women in both the intervention and control groups were included in the trial. The purpose of the present study was to determine whether the magnitude of the changes in total cholesterol (Tc), low density lipoprotein cholesterol (LDLc) and high density lipoprotein cholesterol (HDLc) due to the dietary intervention were dependent on the variation in APOE. Weight, body mass index (BMI), and lipoprotein levels were measured at baseline and at a 6 month follow-up. ANOVA was used to determine whether the change in Tc and LDLc was dependent on dietary intervention and variation at APOE levels. The levels of Tc and LDLc were higher in women with the APOE*4 genotype. There were no statistically significant effects of APOE genotype and changes in Tc and LDLc (P > 0.1). Adjusted Tc and LDLc changes were comparable in the 3 APOE subgroups (Tc = -14.3, -12.9 and -11.7 mg/dl; LDLc = -12.1, -10.7 and -10.7 mg/dl, respectively as above). In conclusion, the genetic (APOE) background of premenopausal women in this study did not have a significant effect on their response to dietary intervention.