High-density (HDL), low-density (LDL) and very low-density lipoproteins (VLDL) have been purified from normal human plasma by a combination of ultracentrifugation in high-density salt and agarose gel filtration. The ability of these lipoproteins to inhibit different molecular weight heparin fractions has been compared, using incubation mixtures comprised of antithrombin III and factor Xa. Residual factor Xa activity was measured using the chromogenic peptide substrate Bz-Ile-Glu-Gly-Arg-pNA. LDL inhibited the high molecular weight (but not low molecular weight) heparin accelerated neutralisation of factor Xa by antithrombin III. VLDL showed a similar, though much reduced anti-heparin activity, while the addition of HDL to the factor Xa incubation mixture produced no measurable anti-heparin activity. These observations suggest that certain plasma lipoproteins may selectively modulate the inhibitory action of heparin against factor Xa.