This study evaluated the effect of entecavir on the pharmacokinetics of adefovir and the effect of adefovir on the pharmacokinetics of entecavir using a fixed-sequence crossover design in healthy adult subjects. Subjects received 10 mg of adefovir once daily on days 1 to 4, 1 mg of entecavir on days 5 to 14, and 1 mg of entecavir plus 10 mg of adefovir on days 15 to 24. Pharmacokinetic assessments were performed on days 4 and 24 for adefovir and on days 14 and 24 for entecavir. The geometric mean ratios (90% confidence interval) for area under the plasma concentration-time curve in 1 dosing interval, peak plasma concentration, and 24-hour postdose plasma concentration of entecavir when coadministered with adefovir and of adefovir when coadministered with entecavir were within the prespecified 0.80 to 1.25 no-effect range. Entecavir and adefovir were well tolerated when administered in combination. Therefore, the pharmacokinetic data generated in this study indicate that entecavir and adefovir can be coadministered without the need for dosage adjustment.