OBJECTIVE: The purpose of this study was to compare the effects of a very-low-fat diet with a low-fat diet supplemented with monounsaturated oil on plasma lipid levels in subjects with hypercholesterolemia. DESIGN: The 8-week study was divided into one 2-week baseline diet and two 3-week intervention periods in a randomized crossover design. SETTING: The study was conducted in an outpatient setting at the Deakin Institute of Human Nutrition, Deakin University, Geelong, Australia. SUBJECTS: Twenty-four free-living subjects with hypercholesterolemia participated in and completed the study. INTERVENTION: After a 2-week baseline period of a self-selected diet, subjects were assigned to one of two dietary interventions: a very-low-fat (10% of energy from fat), high-carbohydrate diet or a low-fat (26% of energy from fat) diet supplemented with olive oil and an olive oil-based margarine. MAIN OUTCOME MEASURES: Lipid measurements included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations. Plasma cholesteryl esters were measured to monitor compliance. STATISTICAL ANALYSES: A paired t test was used to assess differences between treatment periods for each subject. The dependence of the difference between treatment periods on the covariates of age, sex, initial cholesterol concentration, and energy intake was analyzed using repeated measures and analysis of covariance. RESULTS: The low-fat diet supplemented with monounsaturated fat resulted in significantly less high-density lipoprotein cholesterol lowering than the very-low-fat diet (P=.005). Both interventions resulted in significant reductions in both low-density lipoprotein cholesterol and total cholesterol compared with the baseline diet. APPLICATIONS: This study suggests that a low-fat diet enriched with olive oil provides advantages over a very-low-fat diet in the control of serum lipoproteins among persons with hypercholesterolemia.