Alemtuzumab (MabCampath) can purge both B- and T-cells in a variety of clinical situations, as seen in the treatment of autoimmune disorders and of lymphoid malignancies such as B-cell chronic lymphocytic leukemia (B-CLL). One of the characteristics of advanced B-CLL is an increased susceptibility to infection, which may improve in patients whose disease responds to alemtuzumab, particularly when immune reconstitution by non-malignant stem cells is successful. However, at initiation of treatment, patients with advanced disease are likely to have poor immune function, and need careful management during and after treatment. Here, we present results showing the nature of immune reconstitution after alemtuzumab and the ways in which alemtuzumab may affect white cell counts during and after treatment. The management of B-CLL patients is discussed both in the context of minimizing acute "first-dose" events and with reference to the health risks already existing in this patient population. With protocols in place for dose escalation, for dose postponement in the event of cytopenia, and for anti-infective prophylaxis, alemtuzumab can be used effectively and safely in high-risk B-CLL patients.