Both alpha- and beta-calcitonin gene-related peptide (CGRP) exhibit concentration-dependent dual actions upon rat colonic epithelia. At low concentrations (i.e. 0.03-10 nM) both CGRPs produce antisecretory effects that are abolished by pretreating tissues with tetrodotoxin (TTX). At higher concentrations (30-200 nM) secretory responses predominate and these effects are not abolished by TTX. It is suggested that the mediator of the antisecretory actions of CGRPs is somatostatin.