General models of cell activation implicate Ca²⁺ conductance as pivotal in conveying transmembrane signals. During embryonic development, both cell migration and differentiation are influenced by changes in Ca²⁺; and, as a consequence, the modulation of Ca²⁺ is important in the control of many morphogenetic processes. Because Ca²⁺ conductance may be regulated at voltage‐dependent Ca²⁺ channels (VDCCs), we investigated whether neural crest cells develop VDCCs and, if so, whether they function in regulating migration and establishing cytomorphology. Autoradiography indicates that neural crest cells in vitro develop‐L‐type Ca²⁺ channels during migration and differentiation. Blockage of these channels by verapamil, both in vivo and in vitro, leads to a dramatic and reversible inhibition of neural crest migration. Alterations are manifest in vitro in cell‐to‐cell and cell‐to‐substratum contact and in the organization of the actin cytoskeleton. In whole embryos, verapamil or nifedipine inhibits pigment pattern formation. Moreover. blockage of the ‐L‐type Ca²⁺ channels in whole embryos or cultures, after cells have already migrated and differentiated, results in a significant change in individual cell shape and in the overall pigment cell pattern, suggesting further that maintenance of the differentiated state also requires regulation at the ‐L‐type Ca²⁺ channel. Since certain aspects of neural crest adhesion and cytoskeletal function are dependent on Ca²⁺, it is suggested that interactions that regulate the availability of Ca²⁺ through the VDCC may provide coordinate control of motile and adhesive interactions at the cell‐substratum interface.