IFNs potentiate the activity of multiple chemotherapy drugs in vitro; improved activity has been noted with 5-FU and IFN-alpha against colon carcinoma and with IFN-alpha and DTIC against melanoma. The mechanisms whereby interferon potentiates the activity of chemotherapeutic drugs are complex, and different mechanisms may be operative with different drugs and against different tumors. Both indirect immunoaugmentative effects of interferon and direct biochemical modulation of the drugs (as documented in detail with 5-FU) may play a role; further elucidation of these mechanisms will enable us to optimally utilize the combination of interferon and antineoplastic agents.