Abstract: To comparative the antiviral immunomodulatory effect of adefovir dipivoxil and lamivudine in patients with chronic Hepatitis B (CHB) .Two hundred and fourteen CHB patients who underwent a Phase Ⅲ clinical trial of adefovir were investigated.At different time (before therapy, and 4, 12, 24 and 48 weeks after therapy) , the serum HBV DNA values was quantified by real time fluorescent PCR.The serum level of IFN-γ and IL-4 of forty patients selected randomly was determined by specific-ELISA.No significant difference was observed in the serum level of ALT and AST between patients treated with adefovir dipivoxil and those with lamivudine.The serum HBV DNA level with lamivudine therapy decreased more quickly than that with adefovir therapy after 4 weeks (P<0.05) , but the gap vanished at the end point.Meanwhile, the level of serum IFN-γ with lamivudine therapy reached a sighificant peak at 12 weeks, but the level of serum IFN-γ with adefovir therapy improved slowly till the end point (48 weeks after therapy) , which was significantly higher than that before therapy (P<0.05) .The serum IFN-γ values of lamivudine group were higher than that of adefovir group at 4 weeks (P<0.05) , while serum IL-4 values of adefovir group were higher than that of lamivudine group at 48 weeks (P<0.05.The immunity of patients with CHB can be enhanced by the antiviral effect of adefovir or lamivudine, which may arise from the descent of viral load and the restoration of CD4+T cells activity.