The in vitro effect of vasoactive intestinal polypeptide (VIP) on mineralo- and glucocorticoid secretion was investigated in the rat by using adrenal slices, containing zona-medullaris cells, and fragments of adrenocortical autotransplants regenerated from gland capsular-tissue implants, which are completely deprived of chromaffin cells. VIP dose-dependently enhanced basal aldosterone (ALDO) and corticosterone (B) secretions by both kinds of tissue preparations. The maximal effect was observed at a concentration 10(-8) M, but the rise was about 3-fold higher in the case of ALDO secretion by adrenal slices. Corticotropin-inhibiting peptide (CIP), a competitive inhibitor of ACTH, and l-alprenolol (AL), a beta-adrenoceptor antagonist, did not affect basal steroidogenesis of both preparations. CIP (10(-6) M) completely annulled the maximal stimulatory effect of VIP on B production by adrenal slices and ALDO and B secretion by autotransplant quarters, but it did only reduce (by about 50%) that on ALDO production by adrenal slices. AL (10(-7) M) caused a 73% decrease in VIP (10(-8) M)-stimulated ALDO secretion by adrenal slices and when added with CIP (10(-6) M) completely annulled it. In light of these findings, it seems reasonable to suggest that VIP exerts a secretagogue effect on rat adrenal steroidogenesis by a two-fold mechanism: (i) non-specific stimulation of both mineralo- and glucocorticoid secretion by activation of a population of ACTH receptors, and (ii) specific stimulation of mineralocorticoid secretion through the enhancement of catecholamine release by chromaffin cells.