Abstract:During the past 6 years, clinical trials employing α‐interferon (α‐IFN) in hairy cell leukemia (HCL) have shown dramatic improvement in the management of this disease. Complete remissions (CR), however, are relatively rare (10–15%) and a minority of patients (10–25%) do not respond adequately to α‐IFN. The possibility that the poor response to α‐IFN treatment could be related to a peculiar immunological phenotype of the hairy cell (HC) was investigated in this study. The results demonstrated that, in the majority of patients who failed to respond to α‐IFN, HC showed an immunological phenotype characterized by positivity with the CD5 monoclonal antibody which is usually absent on HC and characteristically expressed on B‐chronic lymphocytic leukemia cells. In fact, among the 10 HCL patients who presented with this phenotype, only 5 partial remissions (PR) and 5 minor responses (MR) were achieved, as opposed to the 3 complete remissions (CR), 19 PR and 3 MR observed in the 25 CD5‐negative patients. The possibility that a more extensive immunological analysis of HCL patients at diagnosis may be predictive of the response to IFN t