The insulin-like growth factors (IGFs) are a family of mitogenic proteins involved in the regulation of cell growth and differentiation. The presence and role of the IGF system in oral mucosal epithelium is not clear but could influence our understanding of the pathogenesis of oral cancer. We characterised the expression and function of IGF-1, IGF-2 and IGF receptor in human oral squamous carcinoma cell lines and normal oral epithelial cells as well as normal oral and squamous cell carcinoma tissues. Using reverse transcription followed by PCR, IGF-1 mRNA was only detected in normal cells, whereas IGF-2 and IGF-1R mRNA transcripts were highly expressed in tumour cell lines and tissues. Similar observations were seen by Western blot analysis and immunohistochemistry. Exogenous IGF-2, but not IGF-1, caused significant increases in DNA synthesis in the cell lines. IGF-2 also increased cell proliferation which was significantly attenuated in the presence of an IGF-2 neutralizing antibody or one which blocked IGF-1R. Taken together, these studies suggest that autocrine production of IGF-2, together with over-expression of IGF-1R, may be important components controlling the proliferation of oral carcinoma cells.