rIFN-alpha 2 is an effective substance in the treatment of HCL. Although the complete eradication of hairy cells from the bone marrow is rarely possible, a dramatic improvement of profound cytopenias can be obtained in most patients, 12 out of 13 in this study. The response can be seen after a median treatment duration of about 2 months and appears to be independent of the presence of the spleen. Once a stable improvement of the peripheral blood values is achieved, one dose of rIFN-alpha 2 every other week may be sufficient to maintain the cell counts. The mechanism(s) by which IFN acts remain unclear. We speculate, that HCL is an IFN deficient syndrome because monocytes which are the major source of IFN-alpha are severely depressed in this lymphoproliferative disorder. Following this hypothesis, the IFN therapy would be comparable to the substitution of insulin in diabetic patients.