METHODS Treatment of cutaneous T-cell lymphoma is still a difficult challenge, once the usual therapies (topical chemotherapy, phototherapy, radiation therapy, and chemotherapy) have proved to be unsuccessful. New therapies, mostly immunotherapies, are currently under investigation. The use of recombinant interleukin-2 has already been evaluated in hematopoietic malignancies. We decided to treat patients with advanced cutaneous T-cell lymphoma relapsing or progressing in spite of the usual treatments with high-dose recombinant interleukin-2. Seven patients (three with mycosis fungoides, three with Sézary syndrome, and one with nonepidermotropic large-cell cutaneous lymphoma) were included in this open study. They were scheduled to receive recombinant interleukin-2 at a dose of 20 x 10(6) IU/m2 per day, administered by continuous infusion during three fortnightly induction cycles and five monthly consolidation cycles. RESULTS Three complete responses (two responses to mycosis fungoides; one response to large-cell lymphoma) and two partial responses were obtained. The clinical response appeared after the first cycle of treatment in the good responders. The complete responses are still ongoing 33, 28, and 6 months after completion of recombinant interleukin-2 therapy and without any further treatment. Sequential immunophenotypic studies showed an increase of the CD1+ cells in the dermal infiltrates. No significant modification of natural killer or cytotoxic T cells could be seen. CONCLUSIONS Despite our low number of cases, our results clearly show that some advanced cutaneous T-cell lymphomas can benefit from high-dose recombinant interleukin-2 therapy. Further studies are necessary to determine the exact place of recombinant interleukin-2 in the therapeutic arsenal of cutaneous T-cell lymphoma.