The more effective utilization of well-established chemotherapeutic agents with radiotherapy can be brought to clinical use more rapidly and with greater efficiency than can new agents. New therapeutic approaches to improving cancer treatment will most likely be coordinated with either chemotherapy or radiotherapy or combined chemotherapy and radiotherapy. The results of experimental, theoretical, and clinical studies suggest that the potential for the greatest progress over the shortest period of time in the clinical management of tumors responsive to both treatment modalities lies in the more effective interaction of well-established chemotherapeutic agents with newer radiotherapy schedules in which large amounts of radiation can be delivered between the courses of chemotherapy and temporally separated to minimize toxicity without loss of therapeutic effectiveness. The experimental and theoretical studies reinforce the basic tenets first demonstrated in the clinical management of Hodgkin's disease. This provides the medical framework for more rapidly exploiting the concepts of alternating chemotherapy and radiotherapy in tumors responsive to both treatment modalities and brings options into sharper focus. 1) Either the doses given in radiotherapy or chemotherapy can be increased or the time between treatment modalities or between courses can be decreased. 2) Experimental, theoretical, and clinical results to date provide a rational basis for clinical protocols designed to determine the most effective utilization of these two primary means of cancer management.