To assess the effect of a high monounsaturated fatty acids (MFA) diet on serum lipids, 30 healthy adult normolipidemic volunteers and 37 adult patients with mild hypercholesterolemia (5.4-9.3 mmol/l), 15 of them also with hypertriglyceridemia (2.3-4.8 mmol/l), were studied. Fifteen healthy and 30 hypercholesterolemic subjects (15 of them with associated type 2 diabetes mellitus) received an avocado enriched diet (2000 Kcal, lipids 53% MFA 49 g saturated/unsaturated ratio 0.54), and seven non-diabetic hypercholesterolemic individuals received an isocaloric control diet (MFA 34 g, saturated/unsaturated ratio 0.7). Serum total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride concentrations were measured before and after a 7-day diet period. In healthy individuals a 16% decrease of serum total cholesterol level followed the high MFA diet, while it rose after the control diet (p < 0.001 between diets). In hypercholesterolemic subjects a significant (p < 0.01) decrease of serum total cholesterol (17%), LDL-cholesterol (22%) and triglycerides (22%), and increase of HDL-cholesterol (11%) levels occurred with the avocado diet, while no significant changes were noticed with the control diet. High lipid, high MFA-avocado enriched diet can improve lipid profile in healthy and especially in mild hypercholesterolemic patients, even if hypertriglyceridemia (combined hyperlipidemia) is present.