Since human trophoblast undergoes extensive proliferation and exhibits invasive growth comparable to that of a malignant tumour, human placenta at various different stages of gestation was investigated immunohistochemically with the monoclonal antibody Ab-6 for expression of the p53 tumour suppressor gene. p53 protein was detected in the nuclei of a few trophoblastic cells, almost all belonging to the cytotrophoblast and only very few to the syncytiotrophoblast, in nearly all specimens investigated (first trimester 10/10, second trimester 5/5, third trimester 4/5). First trimester trophoblast exhibited increased expression of p53 protein in the juxtastromal areas of cytotrophoblast cell islands and columns, that is, in areas where high proliferative activity and increased expression of the epidermal growth factor receptor have been described in the literature. Staining was also occasionally seen in trophoblast invading the myometrium. It is most likely that immunohistochemically detectable expression of p53 protein in the trophoblast is due not to mutation of the gene, as in malignant tumours, but rather to up-regulation of the p53 tumour suppressor gene, which could be a mechanism for controlling trophoblast proliferation.