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We report the use of Alemtuzumab (Campath-1H) as salvage treatment in three patients with advanced mycosis fungoides/Sézary syndrome who had previously been treated with conventional chemotherapy. Two patients (case 1 and case 2), aged 42 and 68 yr, respectively, were heavily pretreated (more than three prior therapy regimens, including autologous transplant in case 2) and refractory to conventional chemotherapy, and the third patient (case 3), aged 80 yr, who had refused any chemotherapy, had been resistant to treatment with cyclosporine and steroids. Campath-1H was administered intravenously, after an escalating dose from 3 to 10 mg, at the dose of 30 mg, three times weekly, to a total dose of 1080, 223, and 480 mg, respectively. The patients with Sézary syndrome (case 2 and case 3) showed clearance of circulating Sézary cells and clinical improvement of the skin lesions after 2 wk of treatment. Two patients (case 1 and case 3) completed the treatment (12 and 6 wk) without significant toxicity, the former achieving a partial response and the latter a clinical complete response. The patient (case 2), who suffered from ischemic cardiopathy and diabetes, quickly achieved a clinical improvement of the Sézary syndrome, but he died because of a myocardial infarction after 3 wk of treatment. Our report shows that the treatment with Campath-1H is active even in patients with advanced refractory mycosis fungoides/Sézary syndrome. Further clinical observations on a larger cohort of patients are needed to establish if Campath-1H may have a role as first line therapy in addition to conventional therapy including chemotherapy.