The influence of arginine vasotocin (AVT) on the interrenal secretion of the clawed toad (Xenopus laevis) was studied combining in vivo and in vitro experiments. In vivo: A single injection of 3 nmol AVT per 100 g body weight was given, and the concentrations of corticosterone and aldosterone in the serum were measured after 1, 3, 6, 12, and 24 hr. The serum levels of both steroids remained elevated over 6 hr and declined to normal levels within 12 hr. The increase of the aldosterone concentration was relatively stronger than that of corticosterone. In vitro: A perifusion system was used to study the influence of AVT concentrations ranging from 0.1 to 50 nM on the secretion rates of corticosterone and aldosterone. The response of the interrenals was dose dependent; corresponding to the in vivo results, the elevation rate was higher for aldosterone than for corticosterone. The effects of several nonapeptides were compared. AVT was most effective, followed by mesotocin and arginine vasopressin (AVP). Isotocin and oxytocin had less effect. The selective agonist of the mammalian V2 receptor (1-deamino-8-D-arginine)-vasopressin (DDAVP) did not stimulate the interrenals, while the V1 receptor-selective antagonist ((1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid)-2-(O-methyl)-tyrosine)-AVP could not diminish the stimulation by AVT. Thus, the AVT receptor of the amphibian interrenal must be a special one and is different from the V1 and V2 types of mammals. In a comparison of the effects of AVT with other stimulators such as ACTH(1-28) or urotensin II, it was found that the sensitivity of the interrenals to AVT was similar to that of these peptides. The results indicate that AVT plays an important role in the osmomineral regulation of Xenopus laevis by acting on the corticosteroid secretion of the interrenals.