The cell lines TA3/Ha and TA3/St are derived from the same tumor, grow both in suspension and form liver metastases upon intraportal injection. We have studied the interaction of these cell lines with hepatocytes, which is likely to be relevant for liver metastasis formation. Recently we have shown that the integrin alpha 6 beta 4 is involved in adhesion of TA3/Ha cells to hepatocytes. However, we show here that the alpha 6 beta 4-specific antibodies, that inhibit adhesion of TA3/Ha cells, did not affect adhesion of TA3/St cells to hepatocytes. The beta 4 subunit, present at high levels on TA3/Ha cells, was found to be expressed at a much lower level by TA3/St cells. In contrast, TA3/St cells express much more of the beta 1-integrin subunit than TA3/Ha cells. We assessed whether these differences in integrin expression are responsible for the different adhesion mechanisms used by these cell lines. We show that alpha 5 beta 1, which is expressed by TA3/St cells, and not by TA3/Ha cells, is involved in TA3/St adhesion to fibronectin that is associated with the hepatocyte surface. Since fibronectin is the main extracellular matrix component present on the hepatocyte surface underneath the sinusoidal endothelium, alpha 5 beta 1 may be particularly important for metastasis formation in the liver, as compared to other organs.