Cladribine is a novel drug that selectively depletes lymphocytes and may be able to destroy the activated immunocytes that damage the central nervous system in multiple sclerosis. Our initial controlled studies have shown a beneficial, although temporary, dose-related effect of cladribine on the course of chronic progressive multiple sclerosis. Peak improvement in median Scripps Neurological Rating Scale (SNRS) neurological performance scores, followed by gradual decline, occurred at month 14 after initiation of treatment with a 2.8 mg/kg total dose and at month 7 after initiation of treatment with a 1.4 mg/kg total dose. A marked decrease in the presence of enhanced magnetic resonance imaging lesions was observed at both dose levels. Adverse effects are also dose-related. Mild segmental herpes zoster or transient marrow suppression occurred in some patients treated at the higher total dose, whereas no problems of this kind were observed at the lower total dose. It is our hope that studies that are presently under way will establish cladribine as a practical therapeutic option for patients with all non-benign forms of multiple sclerosis.