The purpose of this study was to examine the association of circulating viral markers with ongoing liver disease in chronic hepatitis B virus infection. Hepatitis B e antigen (HBeAg) was significantly more likely to be associated with abnormal alanine aminotransferase (ALT) activity than was anti-HBe in a group of 102 HBsAg carriers (p less than 0.0001). Within this group, 57 carriers were analyzed for HBeAg, DNA polymerase, and hepatitis B surface antigen (HBsAg) titer, and the relation of each with abnormal ALT was determined. Both HBeAg and elevated DNA polymerase were much more likely to reflect abnormal ALT (p less than 0.00001 and 0.0006, respectively) than did HBsAg titer. Unlike previous studies, higher titers of HBsAg would not be demonstrated in healthy carriers when compared to HBsAg carriers with chronic elevation of ALT; nor were differences in titer appreciated between chronic active and chronic persistent hepatitis. The potential significance of these findings is discussed.