Effects of the addition of serum to the perfusate on hepatic uptake of multilamellar vesicles (MLV) were examined in recirculating perfused rat liver. MLV was labelled with both membrane lipid marker ([14C]cholesteryl oleate) and aqueous phase marker ([3H]inulin or 5(6)-carboxyfluorescein (CF)). The uptake rates of [14C]cholesteryl oleate and CF at 37 degrees C coincided well, indicating both markers to be taken up as MLV. Inulin was released from MLV at 37 degrees C but its uptake rate tended to approach that of [14C]cholesteryl oleate at 4 degrees C or at high MLV dose. Some factor in serum promoted MLV uptake at 37 degrees C, but its effect was inhibited at 4 degrees C. The promoting effect was indicated to be possibly due to activation of adsorption of MLV to the hepatic Kupffer cell surface and/or that of phagocytosis by the cells. The saturation of MLV uptake was observed with increase in MLV dose, suggesting the saturation of MLV adsorption to the hepatic cell or the consumption of serum factor which promotes MLV uptake.