The dose intensity in cancer monochemotherapy is probably the most important prognostic factor. In combination chemotherapy, in which interactions between agents do occur, response, survival, and toxicity might vary between different schedules. In a literature review of all published data of folinic acid and 5-fluorouracil intravenous bolus therapy in colorectal cancer with comparable dose intensity, an attempt was made to characterize the possible differences of the variations of schedules used. The antitumor activity increased significantly from 19% to 30%-35% when the two drugs were used concomitantly in multiple fractions per cycle rather than on a single day. However, fractionation changed the type of dose-limiting toxicity from hematologic and neurologic to gastrointestinal side effects. The different schedules did not differ significantly in the overall frequency of severe toxicities; however, recommending a certain schedule outside of controlled trials should be done cautiously.