Before cells can invade the extracellular matrix, they must alter their expression of adhesion receptors. Syndecan-1 is a cell surface proteoglycan that binds cells to matrix and undergoes changes in expression during development, during differentiation of some cell types, and following malignant transformation in some tumors. To determine if changes in syndecan- 1 expression influence cell invasion, we employed a model system in which human B lymphoid cells invade type I collagen gels. Examination of a panel of cell lines reveals that those lines not expressing syndecan-1 invade and migrate within collagen. In contrast, cell lines expressing syndecan-1 fail to invade. To directly assess the effect of syndecan-1 on invasion, ARH-77 cells, which do not express syndecan-1 and readily invade collagen, were transfected with a cDNA for syndecan-1. The syndecan-1-positive transfectants exhibit a drastically reduced ability to invade as compared to parental cells. This inhibition of invasion by syndecan-1 is reversed by preincubating gels with heparin or by growing cells in chlorate, an inhibitor of glycosaminoglycan sulfation. These results demonstrate that expression of syndecan-1 inhibits cell invasion into collagen and that loss of syndecan-1 expression may be necessary prior to the migration of normal or metastatic cells.