The aim was to compare the effect on atherogenesis of dietary monounsaturated and saturated fatty acids in cholesterol-clamped rabbits. To obtain an average plasma cholesterol concentration of 20 mmol/l in each rabbit during the 13-week cholesterol-feeding period, dietary cholesterol was adjusted weekly. The amount of fat fed daily was 10 g per rabbit in Expts A (n 23), C (n 36), and D (n 58) and 5 g per rabbit in Expt B (n 24). The source of monounsaturated fatty acids was olive oil in all four experiments. The source of saturated fatty acids was butter in Expt A, lard in Expt B, coconut oil in Expt C, and butter or lard in Expt D. Generally, olive oil-fed groups received more cholesterol and tended to have more cholesterol in VLDL and less in LDL compared with groups receiving saturated fat. Analysis of variance of the combined results of all four experiments showed that, in comparison with saturated fat, olive oil lowered aortic cholesterol by 13 (-9-30, 95% confidence interval) % in the aortic arch, and by 10 (-10-26) % in the thoracic aorta, which was not significant. In the comparison with olive oil, no differences in effects on aortic cholesterol content were detected between butter, lard and coconut oil. These findings do not support the view that replacement of dietary saturated fat with olive oil has a major impact on the development of atherosclerosis in addition to that accounted for by changes in plasma cholesterol levels.