Amaranth was an important ancient grain and has current nutritional potential, being high in protein, fiber, lysine, magnesium, calcium, and squalene. Limited, inconsistent evidence demonstrates amaranth grain or oil can lower cholesterol in animal models. In the present study, hamsters received hypercholesterolemic diets consisting of a control, 10 or 20% Amaranthus cruentus grain, or 2.5 or 5% crude amaranth oil for four weeks. Amaranth oil (5%) decreased total and non-high-density lipoprotein (HDL) cholesterol by 15 and 22%, respectively, compared to control. Amaranth grain (20%; providing 1.4% amaranth oil) lowered non-HDL cholesterol and raised HDL cholesterol. Amaranth grain and oil decreased very low-density lipoprotein (VLDL) cholesterol by 21-50%; and increased fecal excretion of particular neutral sterols and the bile acid ursodeoxycholate. Amaranth oil (5%) additionally increased the cholesterol synthesis rate, possibly due to compensatory mechanisms; and decreased hepatic cholesterol ester, indicating reduced cholesterol ester availability for VLDL secretion and consistency with reduced VLDL cholesterol. Amaranth thus affected absorption of cholesterol and bile acids, cholesterol lipoprotein distribution, hepatic cholesterol content, and cholesterol biosynthesis. Amaranth grain and oil did not affect these pathways identically.