Rationale for different chemotherapeutic and radiation therapy strategies in cancer management. The two primary therapeutic strategies in cancer have been to give either chemotherapy and radiation therapy together or give a complete course of one treatment modality before starting the second. Clinical studies show that toxicity has been one of the major deterrents to substantial improvements in cancer management when the two modalities are administered together. On the other hand, the prolonged time necessary to administer all of one modality followed by the other makes it likely that repopulation of the tumor during sequential treatment will diminish therapeutic effectiveness. A third strategy of giving chemotherapy and radiation therapy has been developed. This new regimen was designed to give chemotherapy initially, maintain the chemotherapy schedule to avoid any reduction in its effectiveness, and add radiation therapy as early as possible in between courses of chemotherapy to minimize the development of cross resistance. One of the primary objectives of alternating chemotherapy and radiation therapy is to increase the therapeutic index by reducing toxicity without a significant reduction in therapeutic effectiveness. Recent clinical, experimental, and theoretic results with radiation therapy and chemotherapy for cancer management emphasize the necessity of giving both modalities with the greatest intensity possible in the initial phase of induction therapy. Cancer treatment scheduling determines the toxicity and thereby limits the dose intensity that can be tolerated. Scheduling may also govern the antitumor effect directly; however, normal host tissue makes the determination of the direct effects on the tumor difficult, if not impossible, in clinical studies. Well-defined experimental solid-tumor systems provide the means for determining directly the relationship between toxicity and antitumor effects in relation to tumor burden and total therapeutic dose. In addition, its relationship to dose intensity and scheduling can be determined by the using more sophisticated research techniques, such as response surface methods. Well-defined clinical protocols to determine how to interact chemotherapy with radiation therapy more effectively hold considerable potential for rapid improvement in treatment of radiosensitive and chemosensitive cancers. 