Background We aimed to determine the frequency of alanine aminotransferase (ALT) elevation during interferon-a treatment, the so-called "flare", its relation to serum beta-2 microglobulin levels, and its impact on the outcome of treatment in chronic hepatitis B. Methods. The tiles of 53 treatment-naive patients with chronic hepatitis B (17 hepatitis B e antigen (HBeAg) +ve, 36 HBeAg -ve) who had been treated with 10MU interferon-alpha 2b three times per week for 24 weeks were reviewed. We analyzed the fluctuations in serum ALT, beta(2)-microglobulin, and HBV-DNA levels before, during, and after flare. Results. We detected flare in 4/17 (24%) of the HBeAg +ve and 7/34 (21%) of the HBeAg -ve patients. ALT level peaked between weeks 2 and 16 (mean, week 8). After flare, HBV-DNA disappeared in 5/7 (71%) HBeAg -ve vs 3/4 (75%) HBeAg +ve patients (all seroconverted to anti-HBe). The overall sustained response rate was 41%: 55% in the patients with flare, and 38% in those without (P > 0.05). Basal serum beta(2)-Microglobulin levels were significantly higher in responders vs nonresponders (2.19 +/- 0.32 vs 1.78 +/- 0.34mg/l, mean +/- SD; P < 0.005). In addition, during treatment, serum beta(2)-microglobulin levels increased significantly only in responders, and the degree of increase was significantly higher in responders with flare vs responders without flare (3 +/- 0.33 vs 2.34 +/- 0.35 mg/l; P < 0.001). Conclusions. This study, with a limited sample size, showed that, in chronic hepatitis B, there is a trend for a higher response in patients with exacerbation of hepatitis B with interferon-a treatment. However, the difference does not reach statistical significance to be of predictive value. On the other hand, serum beta(2)-microglobulin levels before and during treatment may be useful in predicting the outcome.