Immunohistochemical staining using three monoclonal antibodies to p53 revealed that most normal human breast epithelial cells (HBEC) in the exponential growth phase, have p53 located in the nucleus but that some cells have the protein in the cytoplasm. Cytoplasmic staining of p53 with the monoclonal antibody PAb240 was inhibited by the specific oligopeptide, NTFRHSVVVP, that corresponds to the amino acids between 210 and 219 in p53 and which includes the epitope domain for PAb240. It was not inhibited by the control oligopeptide SPFVTVHNVR. Growth arrest of HBEC achieved by EGF depletion resulted in predominant nuclear location of p53 and stimulation of arrested cells with EGF induced transient nuclear exclusion of the protein when the induced DNA synthesis level was maximal. These observations suggest that p53 in normal HBEC becomes inactivated by nuclear exclusion during cellular DNA synthesis.