The purposes of this study were (a) to describe the clinical and biochemical manifestations associated with spontaneous reactivation of hepatitis B virus as defined by the reappearance of hepatitis B virus DNA in serum using dot-blot hybridization and (b) to determine whether the clinical and biochemical manifestations associated with hepatitis B virus reactivation were different in patients with and without human immunodeficiency virus-1 infection. During 1 yr, 110 French patients were admitted to Hôpital Beaujon for chronic hepatitis B. Fourteen were found to have hepatitis B virus reactivation; of these, three were anti-human immunodeficiency virus-1-positive. These 14 patients were HBsAg-positive for 60 mo (range = 6 to 180 mo). Clinical manifestations related to reappearance of hepatitis B virus DNA were present in 11 patients. HBeAg/anti-HBe status did not change in nine patients in whom hepatitis B virus reactivation would not have been recognized without hepatitis B virus DNA testing. Cirrhosis was present in nine patients. Four patients, of whom two were anti-human immunodeficiency virus-1-positive, had fulminant liver failure. Two patients died; one was anti-human immunodeficiency virus-1-positive. One patient was given an emergency transplant.