Previous studies have indicated that the nature of the interaction of radiation and Taxol may be dependent on the cell line, drug dose and treatment schedule. The present study represents a systematic attempt to examine the schedule dependence of the interaction of radiation and Taxol in HeLa cells. The protocol used was radiation treatment (7 Gy), followed by a variable interval (0-24 h), followed by exposure to Taxol (7.5 nM, 24 h), followed by plating for a colony-forming assay. Parallel samples were also taken for flow cytometric analysis of the distribution of cells in the phases of the cell cycle at the beginning and end of Taxol treatment. The results indicate that sub-additive, additive or supra-additive interaction can be seen depending on the interval between the radiation and Taxol treatments. Full radiation survival curves were determined for cells exposed to Taxol either immediately or 10 h after the completion of radiation treatment, corresponding to sub-additive and supra-additive interactions, respectively. An examination of the data revealed that maximum cell killing occurred when the percentage of cells in G1 phase was at a minimum at the time of addition of Taxol. Studies of Taxol-induced toxicity using cells synchronized in G1 phase with mimosine and then released and allowed to progress through the cell cycle confirmed this observation. The conclusion of this study is that prior radiation treatment can modify the effect of subsequent Taxol treatment through alterations in the distribution of cells in the phases of the cell cycle. This finding has important implications for the clinical scheduling of these two cancer treatment modalities.