The aim was to determine whether peripheral blood lymphocytes can be used retrospectively to detect hypersensitivity to radiation in breast cancer patients who had exhibited severe reactions to radiotherapy. Blood samples were obtained from patients who developed both acute and late complications. For comparison, samples were also taken from a group of normal individuals, ataxia-telangiectasia (A-T) patients, A-T gene carriers and breast cancer patients previously treated with radiotherapy who failed to develop treatment-related complications. Radiosensitivity was assessed using a limiting dilution clonogenic assay following both high (HDR) and low (LDR) dose-rate irradiation. Following HDR irradiation, only lymphocytes from individuals with A-T were significantly more radiosensitive than those from normal donors. In contrast, at LDR, lymphocytes from A-T heterozygotes and breast cancer over reactors were also, on average, more sensitive than those from normal donors. Lymphocytes from breast cancer patients treated with radiotherapy without developing complications showed no significant differences in radiosensitivity compared with normals. This work has shown that peripheral blood lymphocytes from cancer patients who suffered severe reaction to radiotherapy are, on average, more radiosensitive than those from normal donors, and suggests that lymphocytes may be useful in the future for the development of rapid predictive assays for normal tissue tolerance to radiotherapy.