The hepatic disposition of lactosaminated bovine serum albumin (Lac-BSA) in rats was studied at the whole body, isolated liver, and isolated parenchymal cell levels. After intravenous injection, In-111-Lac-BSA (1mg/kg) was rapidly eliminated from the plasma due to extensive uptake by liver parenchymal cells; however, a significant decrease in hepatic clearance was observed at high dose (50 mg/kg). In a single-pass, constant infusion experiment in the isolated liver, In-111-Lac-BSA was continuously extracted. The extraction ratio at steady state (E(ss)) for In-111-Lac-BSA was significantly decreased by coadministrating galactose, NH4Cl, or chloroquine, and at low temperature, suggesting that hepatic uptake of Lac-BSA proceeds via receptor-mediated endocytosis for asialoglycoprotein. Kinetic analysis of In-111-Lac-BSA binding with isolated parenchymal cells at 4-degrees-C yielded a dissociation constant (K(d)) of 2.5 x 10(-8) M and a value of 3.5 x 10(5) maximal binding sites/cell (B(max)). The internalization rate constant (k(int)) for In-111-Lac-BSA was calculated to be 0.46 min-1 in liver perfusion experiments using the EDTA-wash method.