Besides being an invaluable marker of clonal disease in chronic myeloproliferative disorders (CMPDs), the JAK2 V617F mutation and the mutated allele burden have an impact on disease phenotype and may provide information on prognosis. Recently, hydroxyurea (HU) has been shown to induce a rapid decline in the JAK2 V617F allele burden. The aim of the present study was to assess the dynamics of the JAK2 V617F allele burden during long-term treatment with HU in a series of patients with CMPDs. The JAK2 V617F allele burden was determined by quantitative PCR in 24 patients of whom 17 received HU, four received anagrelide and three were followed without any cytoreductive therapy. During a median follow-up of 24·2 months, no significant reductions in the JAK2 V617F allele burden were seen in patients treated with HU. We conclude that HU has only a limited effect on the JAK2 V617F allele burden in CMPD.