In order to study aortic atherosclerosis and atherosclerotic response to dietary cholesterol and soybean oil in homozygous LDLR-/- mice, the 16 weeks old animals were randomized in 4 groups either fed standard diet (no cholesterol added, group I, 12 male and 12 female), standard diet added 0.5% cholesterol (group II, 12 male and 12 female), standard diet added 10% soybean oil (group Iii, 7 male) or standard diet added 0.5% cholesterol and 10% soybean oil (group IV, 7 male) for 14 weeks. At termination, the plasma cholesterol of males was: 9.4 mmol/I +/- 0.3 (SD) (group I), 34.4 +/- 6.2 (group II), 9.9 +/- 0.07 (group III), 32.6 +/-0.1 (group IV), and of females 6.9 +/- 2.7 (group I) and 31.7 +/- 4.4 (group II). No apparent difference in plasma triglyceride levels was observed between the groups of either sexes. Aortic atherosclerosis (ratio intima/media) in males was 0.17 +/- 0.09 (SD) (group I), 0.96 +/- 0.32 (group II, p<0.05 compared to other male groups), 0.21 +/- 0.09 (group III), and 0.59 +/- 0.34 (group IV, p<0.05 compared to other male groups), and in females 0.12 +/- 0.08 (group I) and 0.83 +/- 0.30 (group II, p<0.05 compared to female group I). No sex difference in the ratio intima/media was recorded for LDLR-/- mice on standard or cholesterol diet. It was concluded that spontaneous hypercholesterolemia and aortic atherosclerosis in LDLR-/- mice were significantly increased by 0.5% cholesterol addition to the standard diet but were not affected by 10% soybean oil addition to the standard diet, and that 10% soybean oil addition to the 0.5% cholesterol diet did not affect cholesterol induced hypercholesterolemia but significantly decreased cholesterol induced aortic atherosclerosis. (C) 1999 Elsevier Science Inc.