The biodisposition of fluorescein-labeled dextrans (FDs) with different molecular weights (MW = 4-500 kDa) was systematically examined in mice. After intravenous injection of FDs at a dose of 120 mg/kg, the levels of FDs in the blood circulation and in the various organs were measured fluorometrically. FDs with a molecular weight lower than 20 kDa showed poor hepatic distribution (2.1-3.7% of dose/g tissue) due to their rapid elimination from the blood circulation. FDs with higher molecular weights were appreciably distributed in the liver (18.9-24.0% of dose/g tissue) and accumulated there over a long period, whereas the FD levels in the other organs were almost negligible a few days after injection. The hepatic mean residence time of FDs ranged from 22.5 to 28.1 d. Partial depolymerization of FDs which accumulated in the liver was observed within 10 d after administration. The hepatic uptake clearance of FDs was decreased with an increase in molecular weight. A marked molecular weight dependency was also seen in the urinary and fecal excretions of FDs. An appreciable dose-dependency was demonstrated in the hepatic uptake of FDs (MW = 40 kDa), as well. The amount of hepatic uptake as a function of dose showed saturation kinetics and was analyzed by a Michaelis-Menten type equation. The apparent values of K(m) (dose) and Vmax (hepatic level) estimated were 116 +/- 5 mg/kg and 1.10 +/- 0.05 mg/g tissue, respectively.