This study evaluated the clinical effect of rIFN-gamma for the treatment of lymphoma and melanoma of the skin by systemic intravenous and intralesional administration. By intravenous drip infusion, one of two cases of mycosis fungoides (stage IV) showed CR of skin lesions by administration of a total of 160 X 10(6) units, 4 or 8 X 10(6) units, every other day for 3 months. The remaining case was, however, in a state of PD. Intralesional administration of rIFN-gamma to six cases of cutaneous lymphoma, including three cases of mycosis fungoides, two cases of cutaneous T cell lymphoma, and one case of adult T cell lymphoma, resulted in three cases of CR, two cases of MR and one case of PD. In contrast, four cases of malignant melanoma, two of which received systemic administration and two intralesional administration, did not show any obvious clinical response, one showing PR and the other three PD. Histopathological examination of skin lesions before and after administration of rIFN-gamma indicated that the cutaneous lymphoma lesions were initially infiltrated by lymphocytes and macrophages, and that later on, they were free from tumor cells. Our study indicates that rIFN-gamma appears to provide a new modality for the treatment of cutaneous lymphoma by systemic and intralesional administration.