Pancreatic fluid and electrolyte secretion was assessed in 56 patients with cystic fibrosis (CF) and 56 non-CF control subjects undergoing pancreatic function testing while stimulated with cholecystokinin and secretin. Both CF patients and control subjects exhibited a wide range of pancreatic function. Fluid and trypsin outputs were positively correlated in both groups. Fluid output in CF subjects was significantly lower, however, than that of control subjects at any given level of trypsin output. Sodium, bicarbonate, and chloride secretions were all significantly decreased in CF subjects. Bicarbonate and chloride were important determinants of fluid secretion, but at any given bicarbonate or chloride output CF subjects secreted significantly less fluid than control subjects. When bicarbonate and chloride were analyzed as simultaneous predictor variables, adjusted fluid secretion was not significantly different in CF and control subjects. Diminished fluid secretion in CF subjects is therefore caused by impaired chloride, as well as bicarbonate, secretion.