Monounsaturated fatty acids in diets are beneficial for the plasma lipoprotein profile, but studies in cell culture point out that they may also be detrimental by inhibiting cholesterol efflux to apo AI.In the present study we used mouse peritoneal macrophages, loaded with cholesterol and upregulated by cyclic AMP or by LXR/RXR ligands and compared the effect of oleic acid on cholesterol efflux to 3 different acceptors. Inhibition of cholesterol efflux by oleic acid ranged from 10 to 25% with HDL or 2.5% mouse serum, while efflux to phosphatidyl choline vesicles was not affected. Previously we reported that the LXR ligand, TO901317, retarded cholesterol removal in vivo from a modified LDL depot in muscle. This could have resulted from inhibition by unsaturated fatty acids or from reduction in macrophage recruitment due to the anti-inflammatory action of LXR.Our current findings, of retardation of cholesterol clearance from the depot in the presence of low macrophage recruitment, support the latter possibility.