Three hundred and eighty-six Chinese patients (262 men and 124 women), age 5-74 years, with chronic hepatitis B virus (HBV) infection were prospectively followed for 1-5 years to determine the incidence, predisposing factors and etiology of acute exacerbations that occurred during the course of chronic HBV infection. Group I consisted of 334 patients with serum alanine aminotransferase (ALT) levels below 200 IU/l at presentation. Of these, 29 (8.7%) patients developed 32 episodes of acute exacerbation during follow-up. The cumulative probabilities of developing exacerbations were 6.3% and 15% at the end of 1 and 4 years, respectively. Group II included 52 patients with ALT levels above 200 IU/l at presentation. Of these, 19 (37%) patients developed 26 episodes of exacerbation during follow-up. The cumulative probabilities of developing eacerbations were 24% and 47% at the end of 1 and 4 years, respectively. In both groups, the probability of developing exacerbations was slightly higher in men and significantly higher in those above the age of 20 and those who were HBeAg positive. Logistic regression analysis showed that HBeAg positivity (p less than 0.00001), elevated ALT levels (greater than 200 IU/l) at presentation (p less than 0.0001) and male sex (p = 0.03) were associated with a significantly higher probability of developing exacerbations. Twenty eight (48%) episodes of exacerbation were accompanied by symptoms of acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)