In response to a diet enriched in saturated fat and cholesterol (CH), male Syrian hamsters develop hyperlipemia and changes of early atherosclerosis. However, it has not been determined if female hamsters are equally susceptible to an atherogenic diet. Male and female hamsters of the F1B hybrid strain (Bio Breeders, Fitchburg, MA) were fed either a chow diet or this diet (HiFat) with added saturated fat (10% coconut oil) and CH (0.05%) for up to 12 weeks. Female hamsters ate significantly more than males, and with the HiFat diet gained threefold more weight than males. However, with the HiFat diet, serum triglycerides (TGs) and CH were markedly increased only in male hamsters. Furthermore, only in males was there a significant increase in stainable fat in the aorta that corresponded to an increase in subintimal foam cells. In freely feeding males, the largest percentage increase in serum CH was in the TG-rich fraction of lipoproteins. After females were castrated, serum TG and CH levels increased to the same extent as in males. These studies demonstrate a profound gender difference in response to an atherogenic diet in these hamsters that has parallels to the lipid patterns of humans and their susceptibility to atherosclerosis.