It has been previously reported that VLDL unbound to monoclonal antibody against apoB-100 was rich in apoE, thus resembling remnant particles (J Lipid Res, 1993:33;369-380). In the current study, we have further analyzed the unbound VLDL fraction in plasma from hypertriglyceridemic patients using a mixture of monoclonal antibodies against apoB-100 and apoA-1. The unbound VLDL isolated from the plasma of hypertriglyceridemic patients was found to be rich in apoE, apoB-48, and triglyceride compared with the bound VLDL. Furthermore, these unbound VLDL, but not bound VLDL, significantly suppressed HMG CoA reductase activity of cultured human skin fibroblasts (-20 to -25%, P = 0.0022). The degree of suppression is significantly correlated with the apoE content of unbound VLDL (r = -0.769, P < 0.05). Unbound VLDL failed to suppress the activity of HMG CoA reductase of LDL receptor negative fibroblasts. These observations indicate a potential atherogenicity of remnant-like unbound VLDL by delivering more cholesterol through the LDL receptor dependent pathway with apoE as a ligand. In conclusion, this new immunoaffinity chromatography system is a useful method for directly quantifying atherogenic remnants in plasma.