Introduction upon chloride secretion, and it is easy to see that Cystic fibrosis (CF), an inherited condition ofunknown-defective'chloride transport might lead to relative cause, is characterized by abnormalities ofelectrolyte, dehydration ofthe luminal surface. Mucus secretions fluid and macromolecule secretion of-exocrine glands. in the4intestine are viscid and crypts appear to be Electrolyte abnormalities in sweat ducts provide distended2, and the high protein concentration ofCF evidence of a secretory defect that appears to affect meconium suggests relative dehydration3. Similarly, all epithelial cells and probably accounts for most of hepatobiliary secretions contain high concentrations the primary pathological lesions affecting a variety ofbile salts, despite'rpduced t6tal bile salt secretion4. of organsincluding the lungs, pancreas, hepatobiliary Furthermore, ourstudies of pancreatic pathology tree, intestine, and vas deferens. Multiple organ suggest that the" complex ductal system of the involvement needs to be explained by the probability pancreas, with it high protein load, and low luminal that a single gene defect accounts for the disease, flow offluid, makes it susceptible toduct obstruction. together with strong physiological and biochemical We will provide data to show that this is a pathoevidence of a primary transport abnormality of logicalfeature ofthis disease. Physiological studies of epithelial tissue involvingan electrogenic chloride the exocrine pancreas in the cat and rabbit, however, channel, or its regulation. suggest that secretin-sti'mulated bicarbonatesecretion Recent exciting discoveries, which show evidence by the pancreatic duct accounts for the majority of of abnormal chloride transport in CF1, raise the fluid secretionu.'Pancreatic bicarbonate secretion is question of how the gastrointestinal tract is affected. diminished in patients with CF, even when pancreatic These effects are summarized in Table 1. Water flux acinar fiunction is within the normal range, suggesting in the small intestine and colon is largely dependent that this defect is not the secondary result of