The migration of human keratinocytes is dramatically influenced by the type of extracellular matrix in contact with the cells: collagen induces the cells to produce long, linear migration tracks. In this study, a migration assay and computer-assisted morphometry were used to quantitate the extent of migration and the linearity of the migration tracks for a variety of cell types. Only human keratinocytes and HT-1080 fibrosarcoma cells produced both high levels of migration (migration index > 30) and highly linear tracks (track linearity > 4.5). Human keratinocytes and HT-1080 cells share at least two other features: both synthesize copious amounts of extracellular matrix components, and both synthesize high levels of collagenase that degrades basement membrane (type IV) collagen. However, zymogram studies of collagenase production do not yield any characteristic collagenase profile which might distinguish these two types of cells from other normal and metastatic cells.