We studied the effects of adefovir or entecavir in six kidney transplant recipients (mean age 45.7 +/- 7.8 yr) who developed hepatitic flare due to lamivudine-resistant hepatitis B virus (HBV) infection, with 18 months of follow-up. All patients had elevated alanine aminotransferase (ALT) levels and HBV DNA >10(5) copies/mL (median 2.15 x 10(8) copies/mL) at baseline. Serum creatinine and creatinine clearance levels were 137.8 +/- 59.7 mumol/L and 62.6 +/- 18.7 mL/min, respectively. Four patients were treated with adefovir and two with entecavir. Median HBV DNA decreased to 1.99 x 10(5) copies/mL (p = 0.028) after six months, 1.5 x 10(4) copies/mL (p = 0.043) after 12 months, and 7.35 x 10(4) copies/mL (p = 0.068) after 18 months of treatment. There was a corresponding improvement in ALT (34.5 +/- 19.1 U/L after 18 months, p = 0.029 compared with baseline). The rate of HBV DNA suppression was variable, and three patients took over six months for the viral load to decrease to <10(5) copies/mL. After 18 months, HBV DNA was <10(5) copies/mL in four patients and <10(2) copies/mL in one patient. Treatment was well-tolerated and renal function remained stable. We conclude that both adefovir and entecavir are effective in the treatment of lamivudine-resistant HBV in renal allograft recipients, and the reduction of HBV DNA to <10(5) copies/mL could be slow.