The effects of insulin (10-1000 microU ml-1) on chylomicron remnant uptake and degradation were studied in hepatocyte monolayer cultures. Both uptake and degradation were stimulated by insulin. The degree of stimulation was influenced by cell density, being most pronounced in sparse cultures. The uptake was stimulated in a dose-dependent fashion and was noticed already at a physiological insulin level (100 microU ml-1). At this insulin concentration uptake was stimulated by approximately 50% (range 26-84%). As suggested by the increase in Vmax for the remnant uptake, the number of lipoprotein receptors on the hepatocytes was increased by 100 microU ml-1 of insulin. Apolipoprotein-E-free low density lipoproteins (LDL) competed much less efficiently for the uptake of radioactive remnants than did unlabelled remnant particles. About half of the stimulatory effect of insulin on the remnant uptake could, however, be abolished by adding an excess of LDL, indicating that at least part of the stimulation by insulin was due to increased activity of the LDL receptor. This study thus shows that physiological insulin levels increase chylomicron remnant uptake in hepatocyte monolayer cultures. It is assumed that the effect of insulin is to increase the number of lipoprotein receptors at the cell surface, and at least part of the stimulation is due to an increase in LDL receptor activity.