The radiosensitivity of murine teratocarcinoma cells was investigated. Our findings are as follows: (1) the undifferentiated teratocarcinoma cells are 3 times more sensitive to UV than their differentiated counterpart and BALB/3T3 cells; (2) X-ray sensitivity of the undifferentiated cells is comparable to that of BALB/3T3 cells; (3) post-irradiation treatment with caffeine strongly sensitizes a fraction of the undifferentiated cells to UV and X-rays resulting in biphasic survival curves of the cells; (4) high UV sensitivity and hyper-sensitization by caffeine is lost upon differentiation of the cells. Possible mechanisms for the unusually high sensitivity of undifferentiated teratocarcinoma cells to radiation and post-irradiation treatment with caffeine will be discussed.