Recombinant human interferon gamma (rIFN- γ) was used for the treatment of 16 patients with various stages of cutaneous T-cell lymphoma (CTCL). All patients had been previously treated with standard topical and/or systemic therapies, and some had received experimental treatment with retinoids, recombinant human interferon alfa-2a (rIFN-α2a), or radiolabeled monoclonal antibodies; most patients had an advanced stage of disease. Objective partial responses (PRs) were noted in five patients (31%) and lasted 3 months to greater than 32 months (median, 10 mo). One of these five patients had previously had disease progression after an initial PR with rIFN-α2a. Six other patients (38%) showed minor or mixed responses. The most common side effects of rIFN-γ included fever, weight loss, mild neutropenia, elevated lac-tate dehydrogenase, and elevated hepatic transaminases. Additionally, one episode of nephrotic syndrome and one cutaneous allergic reaction were noted. None of the toxic effects were life threatening, and all were reversible. These results suggest that rIFN-γhas efficacy in the treatment of CTCL refractory to rIFN-α2a. [J Natl Cancer Inst 82: 208–212, 1990]