BACKGROUND AND AIM: The consumption of olive oil has been associated with lower incidence of cardiovascular disease in the Mediterranean countries. This may be due in part to the action of platelet-activating factor (PAF) antagonists which we have previously demonstrated to be present in olive oil. In order to assess the in vivo effects of olive oil lipids and PAF in the development of atherosclerosis, the effects of diet supplementation with olive oil (OO), olive oil polar lipid extract (OOPLE) and olive oil neutral lipid extract (OONLE) were studied in rabbits fed a cholesterol-enriched diet. METHODS AND RESULTS: Rabbits were fed for 45 days with atherogenic diet (Group A) supplemented with OO (Group B), OOPLE (Group C) or OONLE (Group D). Lipoprotein profiles, plasma in vitro oxidation, blood PAF levels, PAF-induced platelet aggregation and PAF-acetylhydrolase (PAF-AH) activity, were measured on day 0 and 45. Atherosclerotic lesions formed in the aortic wall and wall elasticity were assessed on day 45. Changes in lipid profile were in accordance with previous studies. Blood PAF levels were higher in group A and decreased in group D on day 45. In rabbits fed an atherogenic diet (Group A) blood PAF and PAF-AH increased, atherosclerotic lesions formed and the elasticity of vessel walls declined. In animals fed olive oil (Group B) or OOPLE (Group C) blood PAF-AH increased, platelet aggregation was attenuated, less oxidation occurred in plasma, lesion thickness was reduced and vessel walls retained elasticity. Most of these beneficial changes were not seen in animals fed OONLE (Group D) although blood PAF and plasma oxidation were lower. CONCLUSIONS: The antiatherogenic effects of OO result from OOPLE. The beneficial effect of these factors is linked to PAF metabolism and proaggregant activity.