OBJECTIVE: To report a case of severe stomatitis probably induced by peginterferon alpha-2a. METHODS AND RESULTS: A 42-year-old man with chronic hepatitis C genotype 1b commenced treatment with peginterferon alpha-2a 180 microg subcutaneously weekly and ribavirin 1000 mg/d orally. Twenty-eight days after commencing treatment, the patient experienced difficulties with swallowing, dryness of the mouth, stomatitis, and pain. Diagnosis of stomatitis was made. He did not complain of any other adverse effect of peginterferon alpha-2a and ribavirin. Both medications were discontinued. The withdrawal of peginterferon alpha-2a was followed by the resolution of the oral lesions in three weeks. The patient was followed up in the outpatient clinic at one month and at three months, and he was asymptomatic. CONCLUSIONS: Manufacturers of peginterferon alpha-2a suggest that mouth ulceration, stomatitis, dysphagia, and glossitis are considered adverse reactions of this medication. In this case, the most likely cause of the stomatitis was considered to be peginterferon alpha-2a because of the close temporal relationship between exposure to the drug and onset of symptoms, as well as the rapid resolution of the symptoms and signs after peginterferon alpha-2a was discontinued. An objective causality assessment revealed that a adverse drug event was possible. Clinicians should be aware of this potentially adverse effect of a widely used drug.