Human low density lipoproteins radiolabeled with 125I transfer across confluent monolayers of cultured porcine pulmonary artery endothelial cells. The amount transferred was dependent on the low density lipoprotein concentration and was not saturable at concentrations up to 300 micrograms protein per 0.5 ml medium. Gel filtration showed that more than 90% of the 125I which crossed the endothelial monolayer remained associated with low density lipoproteins, indicating that appreciable amounts of lipoprotein were not degraded during the transfer process. When the endothelial monolayer was exposed for 24 hours to culture media supplemented with 100-300 microM fatty acid complexed with 100 microM albumin, the amount of low density lipoprotein subsequently transferred increased by 65% to 150%. The extent of the increase was dependent on the type of fatty acid added and its concentration. At 200 microM, albumin-bound oleic and linoleic acids increased low density lipoprotein transfer, whereas palmitic, linolenic, arachidonic, and eicosapentaenoic acids did not. These results are consistent with the hypothesis that exposure of the endothelium to elevated concentrations of fatty acid may allow excessive amounts of cholesterol-rich lipoproteins to enter the arterial intima.