In order to analyse the role of the extracellular matrix (ECM) in the migration of oligodendrocyte precursor cells we have used a chemotaxis chamber assay in which the filter separating the wells is coated with different ECM molecules. Two molecules, fibronectin and the laminin family member merosin, promoted migration either alone or in combination with the chemotactic growth factor platelet-derived growth factor. The effects of the ECM molecules and growth factor were additive, and demonstrated that the migrating oligodendrocyte precursors respond both to haptotactic and chemotactic stimuli. A third extracellular molecule, tenascin-C, inhibited migration. This inhibition was substrate-specific; while migration on fibronectin was inhibited there was no effect on merosin-stimulated migration. This specificity confirms that tenascin-C inhibits migration by modulation of individual cell-ECM interactions rather than by a non-specific process of interference with substrate adhesion. An understanding of the role of tenascin-C in central nervous system development will therefore require characterisation of the different colocalising ECM molecules at different developmental stages.