Hexamethylmelamine, mitomycin C and 5-fluorouracil infusion (HexMF) achieved a median survival of 9 months for the 45 patients with either metastatic stage III or unresectable stage II carcinoma of the pancreas. Fifteen percent survived 2 years. Of 32 patients with measurable tumors, 7 had partial and 3 had minor responses (31%); an additional 44% has stable disease for 3 months or more. Response was associated with a 17-month median survival. These findings are indications for further evaluation of both dosage-intensive 5-fluorouracil infusions alone and HexMF as an alternative to streptozotocin- or adriamycin-containing regimens. Patients with nonmeasurable disease are candidates for survival-oriented phase III studies.