One hundred twenty-one patients with advanced measurable adenocarcinoma of the colon were randomized for treatment with intravenous 5-fluorouracil (IV 5-FU) alone, 15 mg/kg/week vs. cytoxan, 15 mg/kg/week IV, on day 1 and 5-FU, 15 mg/kg/week IV during weeks 2--5, repeated in a six-week cycle. Age, sex, performance status, and disease free intervals, were comparable in both arms. Response frequency was 11% for treatment with 5-FU alone and 10% for treatment with combination therapy. The median survival time was significantly greater in the 5-FU-alone arm (8.4 months vs. 5.6 months, P less than 0.05). In both arms, survival was correlated with the nadir white blood count (WBC) achieved during therapy (P less than 0.02). Fourteen patients had pretreatment WBC of greater than 12,000/mm3. None of them had fever, bone marrow involvement with tumor, or recognizable infection at study entry. The 14 patients had a median survival time of 2.3 months, significantly shorter than that of patients with normal pretreatment WBC (P less than 0.05). A pretreatment lymphocyte count was available for all patients. No association between this value and either response to chemotherapy or survival time was noted. These results support the superiority of 5-FU to the combination of 5-FU and cytoxan in the treatment of colon carcinoma, and point to the prognostic significance of the pretreatment WBC in this disease.