CD44 and its variant isoforms are a group of transmembrane glycoproteins which play important roles in immune recognition, in lymphocyte trafficking, and in cell-cell and cell-matrix interactions. Although CD44 is expressed by some normal human epithelial and mesenchymal cells, upregulation of CD44 expression has been related to the metastatic potential of some malignant tumours. In this study of 27 hepatocellular carcinomas (HCCs), an indirect immunohistochemical method was used to investigate the distribution of CD44 in normal liver and to determine whether expression of the standard form of CD44 (CD44s), or two of its variant isoforms (CD44-v3 and CD44-v6), correlated with tumour grade, proliferation indices, or histological evidence of vascular invasion. Fifteen of the tumours were Edmondson grade 11, four were grade 111, and eight were grade IV. Liver cell dysplasia was present in adjacent liver parenchyma in three cases and vascular invasion was observed in ten HCCs. Vascular invasion was found to be more frequent in high grade HCCs and a significant correlation was observed between tumour proliferation indices and vascular invasion. CD44s was not expressed by epithelial cells of normal liver but was expressed by tumour cells in six HCCs; vascular invasion was present in five of these HCCs. Three CD44s-positive cases also expressed CD44-v3 and two of these also expressed CD44-v6. CD44 was not expressed in areas of hepdtocyte dysplasia. There was a significant correlation between CD44 expression and the presence of vascular invasion, hut not between CD44 expression and tumour grade or tumour proliferation indices. It is concluded that upregulation of cell surface CD44 expression on malignant hepatocytes is related to their tendency to vascular invasion and may have implications relating to metastasis and prognosis in patients with HCCs.