Feeding a diet enriched with cholesterol/cholic acid (CCA) to rats caused defective plasma clearance of labeled chylomicron-like emulsions compared with clearance in chow-fed rats. When heparin was injected 5 min before an emulsion, the clearance of the emulsion in CCA-fed rats was significantly improved, and lipoproteins in the remnant and HDL fractions of plasma became enriched in apolipoprotein E. Injection of lactoferrin or poly-arginine inhibited the removal of emulsion or lymph chylomicron cholesteryl oleate in regular chow-fed rats. Poly-arginine but not lactoferrin inhibited the clearance of emulsion or chylomicron triolein also. The results demonstrate the involvement of charge interactions in both the lipolysis and remnant uptake steps of chylomicron clearance.