We examined chemotaxis of human plasma cells (PCs) in response to extracellular matrix proteins (ECMs) in the human PC cell lines FR4ds and OPM-1ds. The FR4ds cells expressed beta 1+, beta 3-, alpha 2-, alpha 3-, alpha 4+, alpha 5+, alpha 6+, and alpha v+ integrins, whereas the OPM-1ds cells expressed beta 1+, beta 3-, alpha 2-, alpha 3+, alpha 4+, alpha 5-, alpha 6+, and alpha v+. Fibronectin (FN) and laminin (LN) promoted the chemotaxis of the PCs. An inhibitory assay with anti-integrin monoclonal antibodies (MoAbs) showed that anti-alpha 4 MoAb partially inhibited the chemotaxis of FR4ds and completely inhibited the chemotaxis of OPM-1ds. Anti-alpha 5 MoAb alone had no effect on either of these two lines. Nevertheless, anti-alpha 5 MoAb completely inhibited chemotaxis when it was added with anti-alpha 4 in FR4ds, demonstrating a novel complementary role of VLA-5 toward VLA-4 in the chemotaxis induced by FN. LN facilitated chemotaxis both in OPM-1ds expressing alpha 3 and alpha 6 integrins and in FR4ds expressing alpha 6 integrin alone. Anti-alpha 6 MoAb completely inhibited FR4ds chemotaxis, whereas anti-alpha 3 and -alpha 6 MoAb had synergistic inhibitory effects on the chemotaxis of OPM-1ds. These results indicated that the distribution of PCs in human tissue are determined by at least two factors: the concentration of the ECM proteins FN and LN and the expression of integrins.