The chemotactic effect of calcitonin (CT) gene products was tested on F9 teratocarcinoma cells, which are an in vitro model of early embryonic development. CT and CT gene-related peptide (CGRP) induce a significant chemotactic response (chemotactic index, 40-50). The order of potency is: chicken CGRP greater than or equal to salmon CT greater than or equal to human CGRP. Human CT is a less potent chemotactic agent (chemotactic index, 15). Compared to other well known peptides with chemotactic activity, such as platelet-derived growth factor (no activity) and transforming growth factor-beta (chemotactic index, 5), CGRP and CT appear to be very active in attracting F9 cells in the Boyden chamber assay. Interestingly, CT and CGRP exhibit little chemotactic effect toward differentiated teratocarcinoma cells (i.e. retinoic acid-treated F9 cells or parietal endodermal PYS cells). While salmon CT and chicken CGRP activate adenylate cyclase activity in F9 cell membranes by 7- to 8-fold, higher concentrations (greater than 10(-10) M) of these peptides are required to stimulate cAMP formation than are required to mediate the chemotactic effect of these peptides. These data imply the possible involvement of CT gene products in regulating cell migration during early embryonic development.