The behavior of cultured neural crest cells of Ambystoma mexicanum and Xenopus laevis in dc electrical fields was studied. In fields of 1-5 V/cm, isolated or confluent cells retract both their anode- and cathode-facing margins. Subsequently, the cells elongate, with protrusive activity confined to their narrow ends. In larger fields (greater than or equal to 5 V/cm), protrusions form on the cathode-facing sides of the perpendicularly oriented cells. The cells then begin migrating laterally, perpendicular to their long axes, towards the cathode. We suggest that the perpendicular alignment and cathode-directed migrations result from cytoskeletal changes mediated by modified ion fluxes through the anode-facing (hyperpolarized) and cathode-facing (depolarized) cell membranes. The breaking of cellular confluence in response to dc electric fields is also discussed.