With the purpose of improving the therapeutic index of [³H] acyclovir (ACV) in the treatment of chronic hepatitis B infection, asialofetuin (AF) which after selective interaction with Ashwell`s receptor specifically enters into hepatocytes, was chosen as a carrier system for hepatic targeting. This drug was first converted to its monophosphate (ACVMP), which was subsequently activated by water soluble carbodiimide to conjugate with ε-NH₂ groups of lysine residues of AF. The molar ratio of ACVMP to AF in the conjugate was 3.9. In rats, elimination of ACVMP-AF conjugate after i.v. injection showed two phase elimination kinetics. Initial apparent elimination rate constant in rats was 0.191 min¹ which was greater than that of ACV. The elimination rate constant from terminal phase was 0.021 min¹. Area under the total radioactivities versus time curve was found to be several times larger in liver than in other organs (spleen, intestine, lung and kidney) after i.v. administration of the conjugate labelled in the drug moiety. The above results suggested that ACVMP-AF conjugate was rapidly taken up by hepatocytes and could be a useful hepatic targeting system.