A 49-yr-old man with chronic hepatitis B manifested hypergammaglobulinemia, lymphadenopathy, and a high serum interleukin-6 level following treatment with recombinant human alpha-interferon. One month later, when the patient was treated with natural beta-interferon, serum levels of interleukin-6 and gamma-globulin increased again. The serum gamma-globulin decreased to the pretreatment level after discontinuation of interferon therapy. The serum alanine aminotransferase level remained normal for 6 months. In this case, hypergammaglobulinemia and lymphadenopathy, as well as the elevated serum interleukin-6 level, were considered to be signs of highly enhanced humoral immunity related to alpha- and beta-interferon therapy.