Despite the paucity of literature dealing with the effect of plasma lipoproteins upon drug disposition, evidence is accumulating that shows that these macromolecular complexes can play important roles in the absorption and transport of lipid-soluble agents. Moreover, preliminary studies have demonstrated that radiotracers can be directed to specific tissues by prior incorporation into the hydrophobic core of specific lipoproteins. Although these studies offer encouragement for the possible use of lipoproteins in the site-specific delivery of radiopharmaceuticals that are used in tracer doses, the use of lipoproteins in the transport of drugs at pharmacological concentrations represents a much greater challenge. Nothing is known at this time about the saturation kinetics of drug incorporation into lipoproteins or partially delipidated lipoproteins. Nor is there any assurance that drug-laden lipoproteins will participate in receptor-mediated uptake processes similar to native lipoproteins. Moreover, receptor-mediated uptake of lipoproteins is a saturable process and may not permit attainment of sufficient drug concentrations within cells. It could be argued, however, that receptor-mediated uptake could be enhanced by prior treatment with hypocholesterolemic drugs as has been shown for cholestyramine. In any event, the possible use of lipoproteins for the site-specific delivery of intravenously administered radiodiagnostics or highly potent drugs (e.g., anticancer agents) appears promising. Only the results of ongoing studies will determine the practicality of this approach.