The interferons represent an important first member of a family of biologic response modifiers used in treating human malignancies. Activities associated with the interferons include inhibition of viral replication, influence on cellular protein production, direct antiproliferative effects, and a variety of modulatory effects on the immune response. These regulatory functions of interferon underlie the interest in its use as an anticancer agent. Interferon alpha is the most extensively studied interferon species. Although antitumor activity has been seen both in vivo and in vitro in some solid malignancies, the most impressive responses have occurred in the hematologic malignancies. For the low-grade non-Hodgkin's lymphomas, response rates of 50%, with 10% to 15% complete responses, have been reported. A response rate of 15% has been reported for chronic lymphocytic leukemia in studies outside of the National Cancer Institute (NCI); in our phase II trials at the NCI, only two (11%) of 18 patients had brief partial responses to recombinant interferon alpha. For patients with cutaneous T-cell lymphomas (mycosis fungoides and the Sézary syndrome), a response rate of 45%, with 10% complete responses, was seen in patients treated with recombinant interferon alpha. Based on such findings, interferon appears to be one of the most effective single agents for cutaneous T-cell lymphomas. Further phase II trials are being conducted to determine whether lower doses of interferon alpha are as effective as the high doses used in the previously reported studies. Phase III trials will involve the use of interferons in combination with chemotherapeutic agents as well as in the adjuvant setting.