Cutaneous T-cell lymphomas are disfiguring malignant lymphoproliferative disorders for which standard therapy has been principally palliative. 2-Chlorodeoxyadenosine (2-CdA), a new purine analogue resistant to degradation by adenosine deaminase that has substantial activity against lymphoid neoplasms, was administered to 16 patients with cutaneous involvement by T-cell lymphoma. All patients had failed topical treatment modalities and/or systemic therapies. Fifteen patients were evaluable; one patient was not evaluable due to incomplete therapy and follow-up. The overall response rate was 47%. Three of 15 patients (20%) achieved complete responses and four of 15 patients (27%) achieved partial responses. The median duration of response was 5 months. One patient remains in unmaintained complete remission at 52+ months. Therapy was well tolerated. Myelosuppression was the principal toxicity encountered, occurring in 8 of 15 (53%) patients. 2-CdA is an effective new agent for the treatment of cutaneous T-cell lymphoma and warrants further study both as a single agent and in combination regimens.