The expression of the oncogene H-ras increases the migratory activity of many cell types and thereby contributes to the metastatic behavior of these tumor cells. On the other hand, several studies point to an involvement of volume-activated Cl- channels (VRAC) in (tumor) cell migration. Here we tested whether VRACs are required for the H-ras-mediated increased migratory activity. We therefore compared VRAC activation and migration of wildtype and of H-ras transformed NIH3T3 fibroblast by means of patch clamp techniques and time lapse video microscopy. Both cell types achieve the same degree of VRAC activation upon maximal stimulation by reducing the osmolarity from 300 mosm/l to 190 mosm/l. However, upon more physiologically relevant reductions of extracellular osmolarity (275 mosm/l), VRAC activation is almost 3 times higher in H-ras fibroblasts. This increased VRAC sensitivity is paralleled by an increased migratory activity of H-ras fibroblasts. Moreover, the high affinity VRAC blocker NS3728 (400 nM) inhibits migration of H-ras fibroblasts by ~50 % whereas migration of wildtype fibroblasts is reduced by only ~30 %. We suggest that H-ras modulates the volume set point of VRAC and thus facilitates transient changes of cell volume required for faster cell migration.