Hydroxyurea (HU) is generally regarded as an effective and well-tolerated drug for the treatment of the chronic myeloproliferative syndromes. It has rarely been implicated as a cause of drug fever. We report two patients with primary thrombocythaemia and one patient with polycythaemia vera who developed fever and shaking chills during treatment with HU. Infection was highly suspected and all patients were examined extensively. The fever subsided after discontinuation of therapy with this drug. However, the fever recurred within 1 day after rechallenge. The mechanism of HU-induced fever remained unclear, but the experience in our patients and the reviewed cases in the literature are highly suggestive of a hypersensitivity reaction. Clinicians should be aware of this rare adverse effect.