Adjuvant chemotherapy has been shown to alter the natural history of resected colon cancer. Two regimens (5-fluorouracil [5-FU] plus calcium folinate and 5-FU plus levamisole [Ergamisol]) have been found to prolong disease-free survival and overall survival in affected patients. Previous comparisons of these two regimens indicate that 5-FU plus calcium folinate may offer a small disease-free survival and overall survival advantage. The demonstration that UFT (uracil and tegafur) plus oral calcium folinate (Orzel) offers significant antitumor activity and an acceptable toxicity profile makes this a logical formulation for the adjuvant treatment of colon cancer. The National Surgical Adjuvant Breast and Bowel Project Protocol C-06 is a randomized comparison of the relative efficacies of 5-FU/calcium folinate vs UFT plus oral calcium folinate. Preliminary analysis of toxicity findings among 473 evaluable patients indicates that both regimens are well tolerated and have similar toxicity profiles. If, in the final survival analysis, UFT plus oral calcium folinate treatment yields the same or better disease-free survival and/or overall survival as the 5-FU/calcium folinate treatment and the toxicity profiles remain similar, it is likely that UFT plus oral calcium folinate will be accepted as a new standard for adjuvant treatment of colon cancer.