Previous studies of patients with the hypereosinophilic syndrome have found very significant morbidity and a high mortality of 77% at 3 years. Our study analyzes the therapy and prognosis of 26 patients with the hypereosinophilic syndrome. Five patients showed no evidence of progressive organ-system dysfunction and were given no therapy; all have done well. Sixteen patients with progressive organ dysfunction were treated with corticosteroids; six of the 16 had a good response and needed no further therapy. Five patients were treated with various chemotherapeutic agents that proved to be ineffective. In eight patients who were unresponsive to corticosteroid therapy, hydroxyurea produced excellent responses in six and partial responses in two. With the above regimen, our 26 patients (including 12 with poor prognostic indicators) have had a marked increase in survival (3-year mortality of 4%) when compared with the historical control group.