A large proportion of a dense subfraction of LDL in plasma is coupled with an increased risk of coronary artery disease, CAD. This may reflect an increased inflow of such LDL subfractions into the intima, since the inflow of lipoproteins is supposed to be inversely related to the size of the particles. In order to evaluate this possibility we used an in vitro perfusion system for aortic intima-media from rabbits with experimental atherosclerosis. The uptake of human VLDL, LDL, HDL and subfractions of LDL (LDL1, 1.019-1.035 and LDL2, 1.035-1.063 g/ml) in lesions and non-involved areas was studied. Our results indicate that particle size is an important factor for the clearance of lipoproteins into the arterial tissue, both for plaques (VLDL 7.6, LDL 25, HDL 58 nl/mg wet wt./h) and in other areas (VLDL 3.8, LDL 4.1, HDL 12 nl/mg wet wt./h). Interestingly, the uptake of LDL2 was as much as 1.5-1.9 times higher than LDL1. This supports the view that an increased lipid load in the arterial wall may be one mechanism behind the association between denser LDL and CAD. Our data also suggest that the difference between LDL uptake in plaque (576 nl/mg wet wt.) and other areas (48 nl/mg wet wt.) not only reflects a rapid clearance but a large distribution volume of the intima (plaque > 60%, non-involved areas 5.7%).