In previous transplantation studies using neural stem cell lines immortalized by the temperature-sensitive SV40 large T-antigen, we have shown that animals with experimental hippocampal lesions resulting from four vessel occlusion recover spatial memory functions more effectively when grafted with the MHP36 cell line than with the MHP15 cell line [Gray et al. (1999). Philos. Trans. R. Soc. London Biol. Sci. 354: 1407-1421]. In the present study, we have investigated the cellular and molecular basis of these differences in repair capacity both in vivo and in vitro. Using the same model of hippocampal damage we have shown that following transplantation MHP36 cells migrate and align within the damaged CA1 of the ipsilateral hippocampus. MHP15 cells, in contrast, migrate in a more indiscriminate pattern that does not reflect the anatomy of the region. To analyze the migratory properties of these two cell lines in more detail, we performed migration assays at a nonpermissive temperature on the extracellular matrix substrates laminin, fibronectin, and vitronectin. These showed that MHP36 cells have a greater migration potential than the MHP15 cells. While the pattern of cell surface extracellular matrix receptors of the integrin family was identical in both cell lines, the different degrees of migration on vitronectin were both blocked by inhibitors of αV integrins. Differences in integrin signaling therefore contribute to the greater migration potential of the repairing MHP36 cell line.