Background. The effectiveness of adjuvant chemotherapy for colorectal cancers after curative resection has been reported recently; this study was performed to clarify the reasons of for this effectiveness, which have been unclear. Methods. Two joint prospective clinical randomized studies were performed. In the first study, of patients operated on between July 1, 1981 and June 30, 1983, at 41 Centers in the Tokai district, 172 patients with colorectal cancer were allocated to two groups. In the control group, mitomycin C (MMC) was given eight times intravenously in the 4 weeks after surgery. The other group, in addition to receiving the same regimen as the controls, received oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) at 600 mg/day for at least 6 months after the 4-week MMC treatment. In the second study of patients operated at 7 Centers in the Tokai district between October 1, 1987 and September 30, 1990, 173 patients with colorectal cancer were allocated to two groups after surgery, a control group receiving no HCFU, the other group receiving HCFU at 0.8 mg/kg per day orally, for 1 year, beginning 4 weeks after the operation. Results. In the first study, the cumulative 10-year survival rate of the MMC + HCFU group was higher than that of the MMC-alone group (P < 0.05). In the second study, the cumulative 5-year disease-free survival rate of the HCFU group was higher than that of the control group (surgery alone; P < 0.05). In patients with colon cancers, the rate of distant metastases for all evaluable patients was lower in the MMC + HCFU group than in the MMC-alone group in the first study (P < 0.05), and the rate was lower in the HCFU group than in the surgery-alone group in the second study (P < 0.02). Conclusion. The effectiveness of HCFU in reducing the disease-free survival rate appeared to be mainly due to its preventive effect on distant metastases.