A 59-year-old man, treated with peginterferon alfa-2b and ribavirin because of a chronic Hepatitis C virus infection presented in the emergency department with acute epigastric pain. An acute pancreatitis, probably toxic, was diagnosed. A literature search confirmed that acute pancreatitis may develop as a result of treatment with (peg)interferon whether or not in combination with ribavirin. It is important to be aware of pancreatitis when patients treated with these medications present with acute epigastric pain. Discontinuing the medication will lead to a rapid reduction of the symptoms and recovery.