In this study, we have analyzed the evolution of serum HBsAg levels in 16 patients with chronic hepatitis B who showed an HBsAg seroconversion following antiviral therapy. The data showed that the clearance of serum HBsAg is slower than that of serum HBV DNA, which may reflect a slow kinetics of clearance of infected hepatocytes. Interestingly, HBsAg was detectable for a longer time using the Architect assay than with the Bio-Rad assay. As viremia suppression is achieved in most patients under therapy with the new generation of nucleoside analogs, these data suggest that the quantitative monitoring of serum HBsAg may represent a novel tool for the assessment of antiviral therapy efficacy. J. Med. Virol. 81:1336–1342, 2009. © 2009 Wiley-Liss, Inc.