The results of treatment with melphalan, vincristine, and 5-FU (MVF) in 32 patients with advanced colonic carcinoma are reported. The objective response rate among 31 patients with measurable disease was 16% (five patients responded). The projected survival for all 32 patients was 277 days. Patients with objective response to MVF had a projected survival of 314 days, significantly longer than the survival of patients with no response to therapy, 84 days (P = 0.01). While toxic effects were mild with MVF, this regimen appears to have greater activity in advanced colonic carcinoma than therapy with 5-FU alone or in combination with nitrosoureas.