Objective: The effect of phytoestrogen intake in combination with estrogen replacement therapy (ERT) on atherogenesis is largely unknown. The aim was thus to study the impact of phytoestrogens alone,or combined with oral estrogen, on experimental atherosclerosis in cholesterol-fed rabbits.Methods: Two separate studies were performed in ovariectomized, cholesterol-fed female rabbits. InStudy A, 45 rabbits were randomized to either a soy-free diet with or without oral 17β-estradiol (E2) 4 mg/day, or a soy-rich diet without any hormone for 14 weeks. In Study B, 100 rabbitswere randomized into five groups (oral E2 0.5, 1, 2 or 4 mg/day, or no hormone) based on a soy-rich diet for 30 weeks.Results: By the end of treatment in Study A, aortic cholesterolcontent was twice the amount in the group treated with the soy-free diet compared with the soy-rich group and with the soy-free plus E2 group (p < 0.001). In Study B, aortic cholesterolcontent showed no significant difference between the groups (ANOVA, p = 0.49), but a tendency towards a lower aortic cholesterol content in the E2-treated animals compared with placebo wasobserved.Conclusion: Dietary phytoestrogens significantly reduce aortic cholesterol content with a potency comparable to that of ERT, and seem to enhance (although mildly) the antiatherogeniceffect of E2 in this model.