We have studied the effect of exogenous calcitonin gene-related peptide on net fluxes of water and electrolytes in the rat small and large intestine. In ligated intestinal loops, intravenous calcitonin gene-related peptide (CGRP) induced colonic fluid secretion but had no effect on the small intestine. Subsequently, using a single-pass perfusion technique, we observed an immediate dose-dependent secretion of water by the rat colon upon intravenous administration of CGRP. Net secretion of sodium, potassium, and chloride were also raised. The implications of these observations for the possible involvement of high circulation concentrations of CGRP in the watery diarrhea syndrome accompanying medullary thyroid carcinoma are discussed.