In vitro studies suggest p53 and bcl-2 may be important in the apoptotic response to irradiation, and that rapidly proliferating cells are more sensitive to radiotherapy. The clinical relevance of biological factors in predicting radiotherapy response was investigated in 62 patients with locally advanced breast cancer. Immunocytochemical staining for p53 protein, BCL-2 protein and MIB 1 antigen on the primary tumour, showed that none of these factors significantly predicted radiotherapy response (BCL-2 p=0.45, p53 p=1.0, MIB 1 p=0.92) and appear to be of no clinical value. A semi-quantitative assessment of MIB 1 staining showed a reduction in positive cells following radiotherapy (p=0.04), consistent with a reduced proliferation associated with response.