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 Hǒpital 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. We conclude that (a) spontaneous hepatitis B virus reactivation is a common complication in white patients infected with hepatitis B virus during adulthood; (b) many cases of reactivation, recognized by reappearance of hepatitis B virus DNA using dot-blot hybridization, would have gone unrecognized if diagnosis had been based only on the reappearance of HBeAg; (c) the clinical spectrum associated with hepatitis B virus reactivation ranges from absence of manifestations to fulminant liver failure; (d) severe liver injury can develop in patients with immune deficiency caused by human immunodeficiency virus-1 infection; and (e) emergency transplantation may be indicated in some patients with hepatitis B virus reactivation and fulminant liver failure (HEPATOLOGY 1990;12:570–574).