(-)-beta-L-2',3'-Dideoxycytidine (beta-L-DDC), (+)-beta-D-2',3'-dideoxycytidine (beta-D-DDC), (-)-beta-L-2',3'-dideoxy-5-fluorocytidine (beta-L-FDDC), (-)-beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine (beta-L-FTC), and (+)-beta-D-1,3-dioxolane-5-fluorocytidine (beta-D-FDOC) were evaluated for their anti-hepatitis B virus (anti-HBV) activities in HBV-transfected human liver cells (2.2.15). The order of decreasing potency for the compounds at the 90% effect level was beta-D-FDOC > beta-L-FTC > beta-L-FDDC approximately beta-L-DDC >> beta-D-DDC. Inhibition of HBV in transfected liver cells by the cytosine nucleosides was selective. The beta-L-nucleoside-5'-triphosphates were consistently more potent inhibitors of woodchuck hepatitis virus DNA polymerase than the corresponding natural beta-D-enantiomers.