Both splenectomy and alpha-interferon are efficient treatments for hairy cell leukemia. Since interferon therapy seems to induce remissions of the disease, avoids the risks of surgery, and sustains the spleen, it should be discussed if this therapy may replace splenectomy as primary treatment for this disease. In order to make this decision the biologic relevance of complete remissions in hairy cell leukemia, the reliability of methods to confirm remission, the benefits and risks of both splenectomy and interferon therapy, and some aspects of the pathogenesis of the disease have to be considered. Based on our experimental and clinical results and data from other groups, we conclude that splenectomy should still be recommended as primary therapy in hairy cell leukemia provided that treatment is indicated and the patient is eligible for surgery.