The cell surface glycoprotein MUC18 was originally identified as a progression associated antigen in melanoma. MUC18 is expressed most strongly on metastatic lesions and advanced primary tumours and is only rarely detected in benign lesions. cDNA cloning revealed MUC18 to be a novel member of the immunoglobulin superfamily with sequence similarity to a number of cell adhesion molecules. Cloning of both the human and mouse MUC18 genes indicate that their predicted protein structures are very similar with an overall amino acid identity of 75%. Like its human counterpart, murine MUC18 is also expressed by transformed melanocytes. Analysis of the promoter region of the human gene has provided evidence for regulatory elements found in smooth muscle specific genes and in both human and mouse: this is the normal site of MUC18 expression. The presence of putative binding sites for the transcriptional factors AP-1, AP-2 and CREB, suggest that MUC18 gene expression can also be modulated by external factors.