Biochemical modulation of 5-FU by leucovorin (LV) has been demonstrated to increase the therapeutic effect compared to single agent 5-FU in the treatment of patients (pts) with advanced colorectal cancer. The purpose of this study was to determine the effectiveness of the 5-FU + LV combination as adjuvant therapy following surgery in pts with Dukes' B, C colon cancer. Pts were entered in a stratified clinical trial comparing two different combination chemotherapeutic regimens to single agent 5-FU, given orally as a control. This report summarized the result of treatment in 61 pts who were 5-FU oral alone and 32 pts who were 5-FU (375 mg/m2) and low-dose LV (20 mg/m2) intravenously for 5 days with 5-FU oral intake. 5-FU with LV regimen was associated with an improved survival compared with the single agent 5-FU oral intake (p < 0.05). 5-FU with LV regimen resulted in less recurrence in liver and lung compared with single-agent 5-FU oral intake.