Neoplasms of possible radiogenic origin developed in two members of a family prone to a diversity of cancers, including bone and soft-tissue sarcoma, brain and breast cancers, and leukaemia. Gamma-irradiation survival studies in these two patients and three other relatives, but not their spouses, over three generations demonstrated resistance to cell killing. The D10 value (radiation dose required to reduce survival to 10%) was significantly higher for the five radioresistant strains (491 +/- 30 rad) than for control cultures (405 +/- 18 rad). There was a significant correlation between individual D10 values and D0 survival-curve parameters, indicating that changes in the exponential slope of the survival curves accounted for much of the increase in D10 values. This novel radiation phenotype could be a manifestation of a basic cellular defect, predisposing to a variety of tumours in family members. Thus in-vitro radioresistance, like radiosensitivity, may be a phenotype of a mechanism that increases cancer risk in man.