Soluble interleukin-2 receptor (sIL-2R) serum levels were evaluated in Sézary syndrome (SS), mycosis fungoides, non-epidermotropic T-cell lymphomas, inflammatory skin diseases (eczema, psoriasis and lichen planus) and benign erythroderma. All groups displayed mean values significantly higher than controls, and values in SS were also significantly higher than those in the other diseases investigated. Follow-up of 17 SS patients showed that serum sIL-2R correlated with the clinical course of the disease and with other haematological parameters (absolute number of circulating Sézary cells, lactic dehydrogenase). Culture experiments demonstrated that, in contrast with other haematological disorders, highly enriched resting Sézary cells were unable to release sIL-2R, and failed to release normal amounts even after mitogen stimulation. Nevertheless, the leukaemic burden, together with the activation and consequent CD25 expression of leukaemic lymphocytes infiltrating the skin, may justify the hypothesis of a neoplastic sIL-2R source. To further support this hypothesis, the highest sIL-2R values were found in patients with advanced disease, in which normal reactive lymphocytes were dramatically reduced.