Abstract: The long chain acyclovir such as the acyclovir laurate and acyclovirpalmitate were prepared directly from acyclovir by application of the usual esterification meth-ods with appropriate acyl chlorides. The lipophilic prodrugs were found to be retained easier byliposomes whereas acyclovir escaped readily from liposomes.When assayed in African green mon-key cell cultures against herpes simplex virus type I strain, the acyclovir palmitate liposomesproved to be more active compared with the parent drug and its liposome, suggesting an en-hanced compatibility between the ester and liposomal lipids and an increased uptake ofencapsulated prodrug by infected cells.