AIM: To determine which baseline factors of chronic hepatitis B patients are predictive of virological response to Peginterferon α-2b therapy. METHODS: A total of 21 HBeAg-positive chronic hepatitis B (CHB) patients treated with Peginterferon α-2b were recruited. They were treated with Peginterferon α-2b (0.5-1.0 µg/kg per week) for 24 wk and followed up for 24 wk. Clinical and laboratory data of the patients were determined at pretreatment and at week 12, at 24 during treatment, and at week 48 during follow up. RESULTS: Ten patients achieved a virological response at the end of treatment. Their baseline serum alanine aminotransferase (ALT), thyroid-stimulating hormone (TSH), and total thyroxin (TT4) levels were significantly different from those who failed treatment. The positive predictive values (PPV) and negative predictive values (NPV) of ALT, TSH, and TT4 were 75% and 89 %, 75% and 89 %, and 75% and 75%, respectively. Moreover, combinations of the baseline ALT and TT4, ALT and TSH, TT4 and TSH levels had much higher PPV and NPV (86% and 88%, 89% and 100%, 83% and 100%, respectively). CONCLUSION: Baseline serum ALT, TSH, and TT4 levels, especially in combination, have high predictive values of virological response to Peginterferon α-2b in HBeAg-positive CHB patients.