We investigated the changes of serum pre-S1 and pre-S2 antigens before and after interferon therapy in 35 carriers with HBeAg, to examine their clinical significance in the therapy. Both antigens were measured quantitatively by solid-phase enzyme immunoassays using monoclonal antibodies specific to each antigen. The titers of these antigens of responders before therapy were significantly lower (p less than 0.001) than those of non-responders (6.23 +/- 1.09 versus 8.65 +/- 2.09 and 4.46 +/- 1.27 versus 6.50 +/- 1.50, respectively). The titers decreased significantly 6 months after interferon therapy in the responders (p less than 0.05), whereas they did not change in the non-responders. Our findings indicate that pre-S1 and pre-S2 antigens have a close correlation with hepatitis B virus replication and are valuable markers for predicting the responsiveness to interferon therapy.