Abstract: Neoglycoalbumin (NGA), a special ligend of asialoglycoprotein receptor on the hepatocyte, was linked via a butanediacyl bridge to acyclovir to form a conjugate NGA-ACV. By using DTA (Differential thermoanalysis ) and HPLC analysis, ACV was shown to be connected with NGA by covalent bonds and stable in blood. The radio biodistribution of ¹³¹I-NGA-ACV with high drug density in vivo was carried out in mice. The maximum absorption of ¹³¹I-NGA-ACV in liver was 81.7±10.4% at 5 min. The radio image of ¹³¹I-NGA-ACV with high or low drug density in rabbit showed no significant difference in liver targeting property. The competitive connection tests indicated that ¹³¹I-NGA-ACV was concentrated in liver through receptor mediated mechanism. A tentative test of antihepatitis B of NGA ACV and ACV in vitro showed that the effective dose of the former was significantly lower than that of the latter.