The factors which lead to the formation of metastases are generally poorly understood; however the expression of a particular variant of the cell adhesion molecule CD44 may be important in facilitating metastasis formation in colon cancer. The aim of the present study was to investigate the expression of CD44 exon v 6 (CD44v6), hyaluronate (one of its ligands), and hyaluronate synthase, in a clinically relevant animal model of metastatic colon carcinoma. HT29 human colon carcinoma cells were injected subcutaneously between the scapulae of severe combined immunodeficient (SCID) mice and left for 3 weeks (by which time the tumours had produced metastases in the lungs). Morphological observations at the tumour-host interface were consistent with the dissociation of neoplastic cells from the primary tumours, and the ability of these cells to migrate through the extracellular matrix facilitating metastasis formation. Immunohistochemically detectable hyaluronate synthase expression was increased in vivo compared with the parent cell line in vitro. CD44v6 expression and hyaluronate were increased around single cells at the periphery of tumours compared with the central regions. CD44v6 and hyaluronate snythase expression were co-expressed in the same cells. Indeed, the present study is the first to demonstrate hyaluronate synthase expression by an epithelial cell type.