Recombinant interferon (rIFN) modulates the cytotoxic effects of the fluorinated pyrimidine, 5-fluorouracil (5FU), in in vitro experimental tumor cell systems. In three clinical trials employing rIFN and 5FU in patients with advanced colorectal carcinoma conducted at the Albert Einstein College of Medicine, more than half the patients achieved an objective response. Of interest, the clinical spectrum of toxicities observed with this combination is different from those seen with either rIFN or 5FU alone. This novel constellation of toxicities includes a clinical syndrome characterized by watery diarrhea followed by life-threatening sepsis. Thus, careful observation and characterization of these toxicities are required. Patient education, with the goal of making patients recognize serious side effects, is important in the management of these patients.