Extracellular matrix has a variety of biological effects on cells, including increased cell adhesion, migration, division and differentiation. Cells are also regulated by soluble factors such as cytokines. We have investigated the binding of interferon-gamma to basement membrane. Interferon-gamma binds basement membrane with a high affinity (kD = 1.5 x 10(-9) M). The binding site is located on the glycosaminoglycan part of the heparan sulfate proteoglycan. This result suggests that extracellular matrix interacts with interferon-gamma and could modulate the cellular response to such factors.