We investigated the effects of radiation on the expression of p53 protein and P-gp in breast cancer cells. Thirty-two preoperatively irradiated surgical specimens of stage I primary breast cancer were examined, and 39 surgical specimens of non-irradiated stage I breast cancer were selected as a control group. p53 and P-gp expression was detected by an immunohistochemical technique using rabbit polyclonal antibodies (RSP-53 and NCL-pGLYPp). The expression of p53 protein, defined as a nuclear immunoreaction in 20% or more of tumor cells, was detected in 4(13%) of the 32 cases in the irradiated group and 7 (18%) of the 39 cases in the non-irradiated group without any statistically significant difference. The expression of P-gp, defined as the presence of strong staining in more than 75% of the tumor cells, was detected in 19 (59%) of the cases in the irradiated group and 12(31%) of the cases in the non-irradiated group. P-gp expression was significantly higher in the former group than in the latter (P <0.05). There was no significant difference in P-gp expression between the stromal invasive component and the intraductal component in either the irradiated or the non-irradiated group. Radiotherapy possibly induces membranous P-gp expression in human breast cancer cells.