Background: Chronic hepatitis B ( CHB) affects 400 million people worldwide and is a major cause of morbidity and mortality. It is known that HBV DNA sequences were detected after the clearance of serum hepatitis B surface antigen ( HBsAg) often in serum, liver and peripheral blood mononuclear cells. The objectives of our study were to evaluate the previous measurements of HBsAg titers versus. quantitative hepatitis B virus ( HBV) DNA and ALT measurements in order to predict the nonresponse and response in interfer-on-alpha (IFN-alpha)- treated HBeAg- positive and HBeAg- negative chronic HBV patients. Methods: We investigate whether the presence of precore mutant affects the response to IFN-alpha therapy and on the titer of HBsAg or not. Twenty-one HBeAg- positive ( group1), 38 HBeAg- negative ( group 2), and 47 healthy inactive carriers ( group 3) made up this study. Liver biopsy showed chronic hepatitis, there was no cirrhosis and none of the patients had IFN-alpha therapy before. Results: The decrease in HBsAg titers was found as statistically not significant in groups 1 ( p = 0.192) and 3 ( p = 0.236) and statistically significant in group 2 ( p = 0.0001) within a 6- month interval. Conclusion: HBsAg titer may be a factor to predict the primary responders and nonresponders specially in HBeAg- negative patients.