During a 6-year (mean 24.5 months) follow-up study of 237 HBeAg-positive patients with biopsy-verified chronic type B hepatitis, 199 episodes of acute exacerbation (SGPT greater than 300 IU/l) were observed in 148 patients. The clinical and laboratory findings of these acute exacerbations were less severe than classic acute viral hepatitis (P less than 0.001) but with remarkable overlapping. The main histological changes of acute exacerbations were those of lobular hepatitis, even with bridging hepatic necrosis which predicted subsequent HBeAg clearance. Anti-HBc IgM was positive in 14.4% of the exacerbations. All of these findings made acute exacerbation of chronic type B hepatitis indistinguishable from acute viral hepatitis aside from chronic clinical history. Hepatitis A virus, delta agent and possibly non-A, non-B virus(es) were responsible for some of the episodes of clinical exacerbations.