Chromosome painting (chromosome in situ suppression hybridization, CISS) analyses were used to control in vitro radiosensitivity of peripheral blood lymphocytes of 70 cancer patients who were assigned to or had just undergone radiation therapy. This technique using three-colour detection of genomic DNA libraries of chromosomes 1, 2, and 4 was shown to uncover reliably radiation-induced chromosome damage in human peripheral blood lymphocytes. The lymphocytes of five out of the 70 cancer patients could be defined as to react hypersensitively to in vitro irradiation. This was particularly underlined not only by the mere increase of aberration rate but also by the quality of the induced abnormalities (e.g. incidence of complex chromosome rearrangements). The same patients were also characterized by extreme radiation reaction in clinical terms. In spite of some confounding factors, based on the presented observations, the CISS-technique can be proposed as a predictive technique for selecting radiosensitive patients and protecting them from undesired side effects of radiotherapy. A simplification of the screening procedure is proposed on the basis of the presented data.