Pancreatic function studies were performed under continuous intravenous stimulation with secretin and cholecystokinin (0.125 mu/kg/min) in 40 patients with CF who had no evidence of steatorrhea and 69 control subjects without CF, who also lacked evidence of steatorrhea. A total of 41 studies in CF patients and 74 in control subjects were analysed for trypsin, electrolyte, and water secretion. 51% of the CF and 51% of the control tests showed trypsin secretion responses between 1000 mu/kg/hr (the lower limit of the normal range) and 2695 mu/kg/hr, while 16.2% of the control tests exceeded this range. Secretion of water and electrolytes, including both chloride and bicarbonate, was significantly lower in the CF subjects when compared to the appropriate controls in the normal and subnormal trypsin output range. Chloride-bicarbonate ratios, although higher in subjects with evidence of pancreatic damage, were identical in CF and control studies. A specific ductal lesion in CF which altered the balance of acinar (predominately chloride) and ductal (predominately bicarbonate) secretion, or encouraged the equilibration of ductal fluid with plasma in the distal ducts, would increase chloride-bicarbonate ratios, as in the subjects with reduced trypsin secretion. Since this did not occur in the patients with normal function, our results suggest that chloride and bicarbonate secretions are impaired to a similar extent in CF, possibly through a dependence on the same phenotypic abnormality.