One hundred and thirty-one thyroid tumours were examined immunohistochemically for expression of retinoblastoma (RB) and p53 protein. The results demonstrate that RB protein is not lost in any cases, indicating that inactivation of the RB gene is unlikely to play a central role in the pathogenesis of thyroid tumours. Eighteen of 24 (75 per cent) undifferentiated carcinomas, 6 of 32 (19 per cent) papillary carcinomas, 5 of 29 (17 per cent) follicular carcinomas, and 6 of 46 (13 per cent) medullary carcinomas showed p53 protein nuclear staining. In 46 per cent of the undifferentiated carcinomas many of the tumour cells had accumulated p53 protein, whereas in the other positive cases less than 5 per cent of the cells had increased p53 protein levels. Our results strongly suggest that p53 protein abnormalities play a crucial role in the progression of well-differentiated to undifferentiated thyroid carcinomas.