To explore genetic effects on the expression of chromosomal fragile sites in vitro, we studied the expression of common fragile sites (c-fra) in cultured lymphocytes of a human chimera (Chi46,XX/46,XY). Since the two cell lines in the chimera share the same environment in vitro and in vivo on cell culture preceding chromosome analysis, differences in the expression of c-fra must be due to genetic factors. The peripheral lymphocytes were cultured in medium 199 and in medium RPMI 1640 with and without aphidicolin. All lesions were localized after GTG-banding and mapped to the human idiogram. In the cultures with aphidicolin the XX cells showed, at high (0.4 microM) APC levels, a significantly higher expression of c-fra than did the XY cells. This difference between cell lineages was not confined to certain individual c-fra; rather it was seen for practically all of them. Therefore, we conclude that there are genetic factors which influence the propensity of c-fra to be expressed. Whether sex is one of these factors, or perhaps even the most important one, still has to be elucidated.