Metastasis represents a major challenge in the therapy of cancer diseases. Migration of tumor cells into the surrounding tissue is an important step within the metastatic cascade. Cell migration and adhesion of human melanoma cells (MV3) are mainly mediated by a2ß1 integrins. The integrin-mediated adhesion to the extracellular matrix strongly depends on the extracellular pH (pH_e). Cell-matrix interactions are promoted by acidic pH_e while they are impaired in an alkaline environment. The present study focuses on the effects of modified ß1-integrin expression on pH-dependent adhesion and migration of MV3 cells. ß1-integrin expression was strongly reduced by employing the si-RNA technique. At ph_e 7.0 reduced ß₁-integrin expression led to decreases in adhesion and migratory speed by 58% and 50%, respectively. These effects could be partially compensated for by extracellular acidification. The cells expressing less ß₁-integrin showed a higher migratory speed under acidic than under alkaline conditions. They were 38% more adhesive and 31% faster at pH_e 6.8 than at pH_e 7.4. In summary, the present findings support our hypothesis that a₂ß₁ integrins mediate cell adhesion and migration in a pH dependent manner.