Tumor cure rates greater than 50% have been realized by the administration of three and four series of 1500 rads radiation and 150 mg/kg (0.9 g/m2) cyclophosphamide which were separated by 1, 7. or 11 days. Increasing the time between treatment modalities from 1 to 7 and 11 days provided a 2- to 3-week recovery period for each treatment modality without a reduction in cure rates. However, the mean time for complete response increased from 24.8 +/- 17 days for 1 day, 30.7 +/- 3.0 days for 7 days, and 38.3 +/- 4.8 days for 11 days between treatment modalities. Giving the second series of radiation and cyclophosphamide on days 16 and 17 resulted in a cure rate of 50%. Increasing this interval to 21-22 days resulted in no cures. The results of giving each modality alone at 11-day intervals have been compared with results of altering administration of the two modalities at 11-day intervals. Comparing the three regimens where a treatment was given every 11 days, the numbers of animals with cures were 0 of 10 for cyclophosphamide alone, 2 of 10 for radiation alone, and 5 of 9 for alternation of the two treatments every 11 days. Well-defined periods of accelerated growth occur between 10 and 20 days after administration of single doses of either radiation or cyclophosphamide. The increased effectiveness of alternate utilization of the two modalities suggests that prior treatment by one modality increases tumor sensitivity to the second modality.