Leu-M1 antigen is a monocyte/granulocyte-related marker known to be consistently expressed in the Reed-Sternberg cells of patients with Hodgkin's disease and to be present in tumour cells of a variety of non-haematopoietic neoplasms, most of them adenocarcinomas. The biological significance of this aberrant reaction has not yet been clarified. Recently, however, we have demonstrated that marked epithelial Leu-M1 immunoreactivity significantly correlated with an unfavourable clinical course in papillary carcinomas of the thyroid gland. The findings of the present study obtained from surgical specimens of 39 tumours suggest that Leu-M1 immunostaining also provides significant prognostic information in patients with medullary carcinoma (MC) of this organ. Irrespective of other morphological and clinical features, local recurrences occurred 2.9 times (P less than 0.005) and death resulting from tumour occurred 4.3 times (P less than 0.03) more frequently among MCs with marked Leu-M1 positivity (greater than 15% tumour cells positively stained) in comparison to tumours with only slight or absent immunoreactivity. A significantly higher recurrence rate of intense Leu-M1-positive MCs was even evident when comparing only tumours of stage pT1-3N0M0 (P less than 0.005). Our findings infer that Leu-M1 immunostaining might be of clinical relevance to the selection of different aggressive adjuvant therapeutic procedures to be used in MCs with high or low malignant potential.