Uptake and degradation of chylomicron remnants by the human hepatoma cell line Hep G2 was studied. Mesenteric lymph was collected from rats and injected into hepatectomized rats to obtain chylomicron remnants. This remnant preparation was taken up and catabolized by Hep G2 cells. The uptake process was dependent on cell growth and was regulated by compactin (a HMG-CoA reductase inhibitor) which suppresses cholesterol synthesis and by mevalonolactone, which enhances cholesterol synthesis. A monoclonal anti LDL receptor antibody blocked binding of chylomicron remnants to Hep G2 cells to a degree, which was comparable to but generally lower than the suppression of low-density lipoprotein binding. The results thus indicate that in Hep G2 cells, chylomicron remnant uptake is regulated, similarly to low-density lipoprotein uptake and that a significant part of the remnant uptake is mediated through the LDL receptor.