The aim of this study was to assess morbidity and the incidence of adverse effects during interferon (IFN)-alpha-2a treatment of patients with chronic hepatitis B. This prospective study included 48 consecutive patients with chronic hepatitis B who underwent IFN-alpha-2a treatment from January 2003 to August 2005. Adverse effects related to IFN treatment were recorded during this period and for 6 mo after treatment. Adverse effects that led to dose reduction or early discontinuation of IFN treatment were examined. Complete response was reported in 25% of patients. At least 1 adverse effect was documented in 88% of patients. Flu-like symptoms were the most frequently observed adverse effects (88%), and thrombocytopenia (63%), leukopenia (54%), and anemia (23%) were also reported. Bleeding occurred in 2 patients. Other adverse effects included neuropsychiatric signs (21%), alopecia (19%), weight loss (17%), thyroid disorders (19%), menstrual cycle irregularities (8%), skin lesions (8%), and dry cough (4%). Adverse effects that led to dose reduction or early discontinuation of IFN treatment occurred in 19% of patients and included impotence, depression, seizure, thyroid disorders, severe thrombocytopenia, and intestinal bleeding. These effects were found to be unrelated to treatment response. No relationship was detected between patient age, duration of treatment, and adverse effects of IFN. Although IFN-alpha-2a treatment induced various adverse effects in patients with chronic hepatitis B, most of these effects were reversible or could be ameliorated. Adverse effects that led to dose reduction or early discontinuation of IFN treatment were found to be unrelated to complete response.