Pregnant females appear to have an increased chromosomal sensitivity to gamma-irradiation. This hypersensitivity was found to parallel the increase of gestation hormone amounts [M. Ricoul, L. Sabatier, B. Dutrillaux, Increased chromosome radiosensitivity during pregnancy, Mutat. Res. 374(1997) 73-78]. An in vitro experiment was developed to study the effect of progesterone. We performed irradiations of whole blood from normal human donors and chromosome were analysed in first generation metaphases. By comparison to untreated controls, all cultures in which progesterone was added around the 24th h of culture exhibited an increased frequency of chromosome rearrangements, principally dicentrics and rings, which confirms the role of progesterone in the results of in vivo studies. BrdU incorporation studies suggested that progesterone was particularly efficient just before the entry into S-phase, which corresponds to the G1/S transition period. Cultures with an increased frequency of chromosome breakage had a slightly higher mitotic index than controls. It is suggested that progesterone may stimulate DNA repair in cells which reached the end of G1-phase with unrepaired breaks. This would allow the cells to enter the S-phase and survive, although some illegitimate repair leads to chromosome rearrangements, visible at the following metaphase.