To evaluate the efficacy and toxcity of Alemtuzumab, an anti-CD52 monoclonal antibody in patients with relapsed or refractory cutaneous T-cell lymphomas and peripheral T-cell lymphomas. Between 2003 and March 2004, 10 previously treated patients with mycosis fungoides (MF; n=4) and peripheral T-cell lymphoma unspecified (PTCLU) with nodal involvement (n=6) were enrolled onto a phase II trial and treated with Alemtuzumab in our Institute. This monoclonal antibody was given at a dose of 10 mg 3 times a week for 4 consecutive weeks. Of the 10 patients, 2 (20%) achieved complete response (CR), 4 (40%) partial response (PR), and the remaining 4 showed no benefits from the treatment. In the MF subset were observed only PR (3/4, 75%), while in the PTCLU patients there were 2 (33%) CR and 1 (17%) PR, respectively. The durations of CRs were 3 and 8 months. Treatment was well tolerated; hematolgic toxicity was mild. In terms of infectious adverse events, cytomegalovirus reactivation occurred in 1 (10%) patient and none patient had additional suspect or manifest infection. The results of the present phase II study show activity of Alemtuzumab as a single agent in patients with pretreated CTCL and PTCL using a low dose schedule; at the same time, this efficacious reduced dose permitts to avoid treatment-related mortality and to curtail the CMV reactivation rate.