We conducted a 12-month longitudinal investigation of the subtype-dependent response of hepatitis B virus (HBV) to lamivudine treatment in 43 consecutive patients with chronic hepatitis B. HBV subtype ayw appears to respond better to lamivudine monotherapy than does HBV subtype adw (P=.005). This might be the reason for the lower incidence of lamivudine-resistant strains observed in persons infected with HBV subtype ayw during follow-up.