Since alfalfa meal prevents hypercholesterolemia and atherosclerosis in rabbits and alfalfa saponins prevent the expected rise in cholesterolemia induced by dietary cholesterol in monkeys, the experiments being reported here were performed to determine whether alfalfa saponins affect atherogenesis in rabbits. In addition, the effects of alfalfa seeds were studied. Cholesterol-feb rabbits were randomly assigned to 3 groups: (a) control animals (N = 18); (b) animals maintained on a diet containing 1.0 to 1.2% alfalfa saponins (N = 18); and (c) animals maintained on a diet containing 40% alfalfa seeds (N = 17). Results after a 4-month observation period demonstrated that alfalfa saponins and alfalfa seeds reduce hypercholesterolemia, aortic sudanophilia, and the concentration of cholesterol in aortic intima-plus-media and in the liver, but do not induce changes in the hematocrit.