Recent findings Indicate that variable expression of β Integrins may play a role In differential melanoma cell motility. Primary melanoma (PM) and metastatic melanoma (MM) cultures, derived from the same patient, were tested for their β1, α2, α3, and α6, Integrln subunlt expression and cell migration on type IV collagen (CN IV) or lamlnln (LN). The MM cell line expressed markedly Increased levels of the β1, α2 and α3, but not α6 subunlt compared to the PM cell line. The MM cell migration rate was significantly higher than that of the PM cell line on LN- or CN IV-coated substrates. Furthermore, the cell migration rate of both lines was significantly higher (p < 0.001) on these substrates than on the control substrates. The MM and PM cell migration was significantly Inhibited by function-blocking antl-β1 and anti-α3 MAbs, but not by the antl-α6 MAb tested. In contrast, the anti-α2 MAb significantly Inhibited MM but not PM cell migration. These data show that the α3 subunlt plays a significant role in melanoma cell motility on CN IV and LN and that. the α3 subunlt has a significant contribution to the motility of the MM cell line.