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 (VD-CCs), 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.