We have previously shown that calcitonin gene-related peptide (CGRP) stimulates the secretion of corticosterone and aldosterone from the frog adrenal gland in vitro. The aim of the present study was to investigate the role of cytoskeletal elements in the stimulatory effect of CGRP on corticosteroid production. Perifusion of adrenal explants with the microfilament-disrupting agent cytochalasin B (5 10 - 5 M) induced a reversible inhibition of the spontaneous secretion of corticosterone and aldosterone, and markedly reduced the stimulatory effect of frog CGRP (3 10 - 7 M) on corticosteroid release. In contrast, administration of the antimicrotubular agent vinblastine (10 - 5 M) and the intermediate filament inhibitor β-β iminodipropionitrile (10 - 3 M) had no significant effect on either spontaneous or CGRP-evoked steroid secretion. Taken together, these data provide the first evidence for the involvement of microfilaments in CGRP-induced corticosteroid secretion. In contrast, microtubules and intermediate filaments are not implicated in the mechanism of action of CGRP.