A spontaneous change of cellular DNA content occurred in a hyperdiploid human colonic carcinoma grown in nude mice. After the change to hyperpentaploidy the tumor was exposed to single-dose X irradiation, and the effects on growth curves and on the cell cycle, determined by flow cytometric DNA analysis (FCM), were compared to results obtained with the tumor prior to the evolutionary event. The results showed that the radiation effects on growth rate and on cell kinetics had changed after the change in cellular DNA content. In the hyperpentaploid tumor the irradiation had no effect on the regrowth rate, whereas in the hyperdiploid tumor the postirradiation growth rate had decreased. As a consequence of the different effect on the regrowth rate of the tumors the growth delay was inadequate as a parameter for comparing the radiosensitivity. In the hyperpentaploid tumor the irradiation induced a partial synchronization of accumulated cells, whereas no synchronization effect was found in the hyperdiploid tumor. The redistribution time was 8-10 days for both tumors. The results indicate that clonal evolution may affect radiosensitivity, and that FCM analysis may prove to be a valuable method to provide rapid information on cellular synchronization and on redistribution time.