In vivo effect of a bolus combination with 5-fluorouracil (5-FU) and CPT-11 was studied against experimental rat lung cancer, SLC cells. 5-FU and CPT-11, when administrated individually, showed dose-dependent inhibition against the tumor (ID50, 7.0 mg/kg/day and 16.0 mg/kg/day, respectively). 5-FU synergistically enhanced the sensitivity of the tumor cells to CPT-11 and permitted the administration of approximately a one-third lower dose of CPT-11 to obtain the same inhibition against the tumor cell growth. The ID50 of CPT-11 alone (16.0 mg/kg/day) was reduced to 4.8 mg/kg/day when combined with 5-FU at 2.5 mg/kg. There were no deaths caused by toxicity in the combination group, and for lower doses (less than 4 mg/kg/day) of CPT-11 combined with 2.5 mg/kg/day of 5-FU, all rats showed less than 10% body weight loss at the end of the experiments. When the tumor weights were evaluated by using isoeffect plot analysis, the data points resulting from the combination showed a synergistic interaction between these agents. There was no significant increase of toxicity as assessed by the body weight. The results might support for the use of the combination of 5-FU and CPT-11 in cancer chemotherapy.