Specificity of two intestinal ion transport systems toward the natural peptide hormone analogs somatostatin and urotensin II has been demonstrated by electrophysiological and radiotracer studies in vitro. Somatostatin inhibits active C1 secretion across the theophylline-treated rat colon but urotensin II, a dodecapeptide somatostatin analog from the teleost caudal neurosecretory system, is without effect. Conversely, urotensin II stimulates active Na and C1 absorption across the posterior intestine of the 5% seawater-adapted goby, Gillichthys mirabilis, but somatostatin is ineffective. From these and others' studies, it appears that in both systems, increased net absorption results from increased mucosal-to-serosal unidirectional ion fluxes. Based on structure-activity relationships in these and other systems, it is speculated that the difference in amino acid residues at position 4 (somatostatin-Lys, urotensin II-Ala) may contribute to the observed specificity.