Five hundred twelve (373 men, 139 women) patients, aged 1-75 yr, with chronic hepatitis B virus infection seen during a 5-yr period were analyzed. Of these, 43.8% were hepatitis B e antigen (HBeAg)-positive, 49.2% were positive for hepatitis B e antibody, and 7% were negative for both HBeAg and hepatitis B e antibody at presentation. The cumulative probability of clearing HBeAg at the end of the first, second, and third years was 17%, 30%, and 34%, respectively. The probability of clearing HBeAg increased with the age of the patients. Reversion to HBeAg occurred in 7.8% of patients who were HBeAg-negative at presentation and 32.3% of HBeAg-positive patients who cleared HBeAg. In 70.6% of these patients, serum hepatitis B virus-deoxyribonucleic acid was persistently positive or became detectable at the time of HBeAg reversion. Most reversions occurred during the "e-window" phase. The reversions were transient in 31.8% of the cases. Recognition of the dynamics of these serologic changes is important in the evaluation of therapeutic regimens aimed at suppression of HBV replication and call for controlled trials with adequate duration of follow-up. Biochemical exacerbation of liver disease accompanied 38.7% of HBeAg to hepatitis B e antibody seroconversions and 34.8% of reversions. Such exacerbations may be mistaken for acute attacks of hepatitis B in patients not previously recognized to be hepatitis B surface antigen carriers and, in the absence of serial serologic data, are indistinguishable from superimposed non-A, non-B hepatitis.