AIMS:It has been proposed that in-vitro measurements of radiosensitivity might allow individualisation of patient radiotherapy schedules, with concomitant increases in the therapeutic ratio between tumours and normal tissues. Most predictive assay research on normal tissues to date has been based on the radiosensitivity of normal lymphocytes and skin fibroblasts as determined by clonogenic cell-survival assays. Studies comparing the radiosensitivity of fibroblasts or lymphocytes with acute or late radiation damage have reported variable results. METHODS:In this study, we measured the radiosensitivity of lymphocytes from three patients displaying clinical radiation hypersensitivity who were known or suspected to carry germline mutations in genes that have been linked to increased radiosensitivity (a BRCA2 mutation carrier, a patient with Bloom's syndrome and a patient with a Fanconi anaemia-like condition), to investigate whether there is a correlation between cellular radiosensitivity and normal tissue response. RESULTS:We found no association between lymphocyte radiosensitivity and the development of adverse radiation reactions in this group of patients, as is observed in the paradigm radiosensitivity syndrome, ataxia-telangiectasia. CONCLUSIONS:Our results, and those of others, show that, at present, the evidence is not strong enough to justify routine clinical use of clonogenic cell survival assays to predict radiation response.