Two patients showed an unusual serologic response to hepatitis B virus infection during intensive chemotherapy for acute lymphoblastic leukemia. Before treatment, one patient was anti-HBs- and anti-HBc-positive. During intensive chemotherapy these antibodies disappeared and HBsAg and HBeAg became detectable. Twenty months later, still on maintenance chemotherapy, active viral replication with high DNA polymerase levels was present. The second patient developed anti-HBc during the first course of intensive chemotherapy for acute lymphoblastic leukemia. She had anti-HBc and anti-HBe when a bone marrow relapse of the leukemia was diagnosed 3 years later and became HBsAg-positive together with high DNA polymerase levels in the serum while receiving intensive chemotherapy. Clinically no signs of active hepatitis were noted in these patients.