The diagnosis of HBV reactivation during cytotoxic chemotherapy is based on an abrupt rise in levels of serum HBV DNA in conjunction with a hepatitic picture and in the absence of other causes of hepatitis. However, several cases of “hepatitis” have been noted during chemotherapy in HBsAg-positive patients, for which no cause could be found and in which HBV DNA levels were negative. One possible explanation is that HBV reactivation may, indeed, have been the cause but that HBV DNA levels became negative by the time ALT levels peaked and the clinical diagnosis of hepatitis was made. During the course of a longitudinal study of HBsAg-seropositive cancer patients who were monitored during standard chemotherapy, the opportunity was available to test this hypothesis. J. Med. Virol. 65:473–477, 2001. © 2001 Wiley-Liss, Inc.