A 39-year-old woman presented to the emergency room with fever and tender swollen neck two days after the first injection of Peginterferon alpha-2a (Pegasys). She had been under Interferon therapy for melanoma over the last five months. Because of side effects Interferon alpha-2a (Roferon-A) was discontinued and she was given Peginterferon alpha-2a. On examination, she was unwell, febrile (38.8 degrees C) and her pulse was 110/min. Laboratory findings were as follow: erythrocyte sedimentation rate 85 mm/h, C-reactive protein 143 mg/L, white cell count of 11 x 10(9)/L (3.0-9.6), TSH 0.10 mU/L (0.27-4.20), fT4 24.2 pmol/L (12-22), fT3 5.5 pmol/L (2.8-7.1) antinuclear antibodies 1:80, antithyreoglobulin antibodies 212 IE/ml (< 100), thyreoglobulin 442 microg/L, anti-TPO normal and TSH receptor antibodies were negative. Ultrasonography revealed an enlarged, focally hypoechoic thyroid. We suspected she had a Peginterferon alpha-2a induced thyroiditis de Quervain and started a therapy with NSAR and thereafter with Prednison 20 mg. Her symptoms resolved within few days. Thyroiditis in association with Interferon alpha-2a have already been reported. Not known is, to our knowledge, an acute thyroiditis as a side effect of treatment with Peginterferon alpha-2a. Our case shows that also Peginterferon alpha-2a can induce an inflammation of the thyroid similar to de Quervain's thyroiditis.