AbstractThe interaction of lymphocytes with the extracellular matrix plays an important role in the immune defence against tumor cells and virus‐infected cells. We have examined the effect of matrix proteins on the migration of large granular lymphocytes (LGL) through 3‐μm pores in Nuclepore filters in a Boyden invasion chamber. Fibronectin bound on the filter surface significantly increased (p<0.001) the capacity of LGL to migrate, whereas soluble fibronectin did not. In addition, a significantly higher (p<0.001) percentage of LGL was capable of migration through fibronectin‐coated filters than through untreated filters. With fibronectin‐coated filters, a strong enrichment of CD16+and CD56+CD3−cells with LGL morphology and reduction of CD3+cells was found among migrating cells when the incubation time was 4 h or less. Later agranular lymphocytes, mainly CD3+T lymphocytes, also started to migrate. Laminin coating of filters also facilitated migration, and when filters were coated with both fibronectin and laminin the increase in migration was equal to the sum of the increases induced by each protein alone. Interactions between cell surface and the Arg‐Gly‐Asp (RGD) peptide sequence of many matrix proteins had no role in the LGL migration through untreated flters. However, when filters were coated with either fibronectin or laminin, or with both, peptide containing the RGD sequence reduced migration to the level of untreated filter, whereas an Arg‐Gly‐Glu control peptide had no effect. Our results show that unstimulated LGL/natural killer cells are capable of rapid migration through matrix‐coated porous membranes, and that interactions between cell surface receptors and the RGD sequence of fibronectin and probably laminin are util